@Article{ EggerSWSOK2015, title = {Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2015}, month = {11}, volume = {112}, number = {45}, pages = {14072–14077}, abstract = {Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs. To do so we combined in vivo electrophysiology and morphological reconstructions with computational modeling. We show that whisker-evoked membrane depolarization in L2 PNs arises from highly specialized spatiotemporal synaptic input patterns. Temporally L1 INs and L2–5 PNs provide near synchronous synaptic input. Spatially synaptic contacts from L1 INs target distal apical tuft dendrites, whereas PNs primarily innervate basal and proximal apical dendrites. Simulations of such constrained synaptic input patterns predicted that inactivation of L1 INs increases trial-to-trial variability of whisker-evoked responses in L2 PNs. The in silico predictions were confirmed in vivo by L1-specific pharmacological manipulations. We present a mechanism—consistent with the theory of distal dendritic shunting—that can regulate the robustness of sensory-evoked responses in PNs without affecting response amplitude or latency.}, web_url = {http://www.pnas.org/content/112/45/14072.full.pdf}, state = {published}, DOI = {10.1073/pnas.1518773112}, author = {Egger R{regger}; Schmitt AC{aschmitt}{Research Group Neural Population Imaging}; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Sakmann B; Oberlaender M{moberlaender}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ HelmchenDK2013, title = {Miniaturization of two-photon microscopy for imaging in freely moving animals}, journal = {Cold Spring Harbor Protocols}, year = {2013}, month = {10}, volume = {2013}, number = {10}, pages = {904-913}, abstract = {This article describes the development and application of miniaturized two-photon-excited fluorescence microscopes ("two-photon fiberscopes"). Two-photon fiberscopes have been developed with the aim of enabling high-resolution imaging of neural activity in freely behaving animals. They use fiber optics to deliver laser light for two-photon excitation. Their small front piece typically contains a miniature scanning mechanism and imaging optics. Two-photon fiberscopes can be made sufficiently small and lightweight to be carried by rats and mice and to allow virtually unrestricted movement within a behavioral arena. Typically mounted to the animal's skull above a cranial window, two-photon fiberscopes permit imaging of cells down to at least 250 m below the brain surface (e.g., in rat neocortex). In freely exploring animals, action-potential-evoked calcium transients can be imaged in individual somata of visual cortex neurons bulk-labeled with a calcium indicator. Two-photon fiberscopes thus enable high-resolution optical recording of neural activity with cellular resolution during natural behaviors.}, web_url = {http://cshprotocols.cshlp.org/content/2013/10/pdb.top078147.full}, state = {published}, DOI = {10.1101/pdb.top078147}, author = {Helmchen F; Denk W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ WallaceGSRNK2013, title = {Rats maintain an overhead binocular field at the expense of constant fusion}, journal = {Nature}, year = {2013}, month = {6}, volume = {498}, number = {7452}, pages = {65–69}, abstract = {Fusing left and right eye images into a single view is dependent on precise ocular alignment, which relies on coordinated eye movements. During movements of the head this alignment is maintained by numerous reflexes. Although rodents share with other mammals the key components of eye movement control, the coordination of eye movements in freely moving rodents is unknown. Here we show that movements of the two eyes in freely moving rats differ fundamentally from the precisely controlled eye movements used by other mammals to maintain continuous binocular fusion. The observed eye movements serve to keep the visual fields of the two eyes continuously overlapping above the animal during free movement, but not continuously aligned. Overhead visual stimuli presented to rats freely exploring an open arena evoke an immediate shelter-seeking behaviour, but are ineffective when presented beside the arena. We suggest that continuously overlapping visual fields overhead would be of evolutionary benefit for predator detection by minimizing blind spots.}, web_url = {http://www.nature.com/nature/journal/v498/n7452/pdf/nature12153.pdf}, state = {published}, DOI = {10.1038/nature12153}, author = {Wallace DJ{dhw}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Sawinski J{jsaw}{Research Group Neural Population Imaging}; Rulla S{rulla}{Research Group Neural Population Imaging}; Notaro G{gnotaro}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ PawlakGSGK2013, title = {Changing the responses of cortical neurons from sub- to suprathreshold using single spikes in vivo}, journal = {eLife}, year = {2013}, month = {1}, volume = {2}, pages = {1-18}, abstract = {Action Potential (APs) patterns of sensory cortex neurons encode a variety of stimulus features, but how can a neuron change the feature to which it responds? Here, we show that in vivo a spike-timing-dependent plasticity (STDP) protocol—consisting of pairing a postsynaptic AP with visually driven presynaptic inputs—modifies a neurons' AP-response in a bidirectional way that depends on the relative AP-timing during pairing. Whereas postsynaptic APs repeatedly following presynaptic activation can convert subthreshold into suprathreshold responses, APs repeatedly preceding presynaptic activation reduce AP responses to visual stimulation. These changes were paralleled by restructuring of the neurons response to surround stimulus locations and membrane-potential time-course. Computational simulations could reproduce the observed subthreshold voltage changes only when presynaptic temporal jitter was included. Together this shows that STDP rules can modify output patterns of sensory neurons and the timing of single-APs plays a crucial role in sensory coding and plasticity.}, web_url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552422/pdf/elife00012.pdf}, state = {published}, DOI = {10.7554/eLife.00012}, EPUB = {e00012}, author = {Pawlak V{vpawlak}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Sprekeler H; Gerstner W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ KerrN2012, title = {Functional imaging in freely moving animals}, journal = {Current Opinion in Neurobiology}, year = {2012}, month = {2}, volume = {22}, number = {1}, pages = {45–53}, abstract = {Uncovering the relationships between animal behavior and cellular activity in the brain has been one of the key aims of neuroscience research for decades, and still remains so. Electrophysiological approaches have enabled sparse sampling from electrically excitable cells in freely moving animals that has led to the identification of important phenomena such as place, grid and head-direction cells. Optical imaging in combination with newly developed labeling approaches now allows minimally invasive and comprehensive sampling from dense networks of electrically and chemically excitable cells such as neurons and glia during self-determined behavior. To achieve this two main imaging avenues have been followed: Optical recordings in head-restrained, mobile animals and miniature microscope-bearing freely moving animals. Here we review progress made toward functional cellular imaging in freely moving rodents, focusing on developments over the past few years. We discuss related challenges and biological applications.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0959438811002200}, state = {published}, DOI = {10.1016/j.conb.2011.12.002}, author = {Kerr JND{jkerr}{Research Group Neural Population Imaging}; Nimmerjahn A} } @Article{ MeyerSWSKSH2011, title = {Inhibitory interneurons in a cortical column form hot zones of inhibition in layers 2 and 5A}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2011}, month = {10}, volume = {108}, number = {40}, pages = {16807-16812}, abstract = {Although physiological data on microcircuits involving a few inhibitory neurons in the mammalian cerebral cortex are available, data on the quantitative relation between inhibition and excitation in cortical circuits involving thousands of neurons are largely missing. Because the distribution of neurons is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than to rely on sparse sampling methods. Here, we report the comprehensive mapping of interneurons (INs) in cortical columns of rat somatosensory cortex, immunolabeled for neuron-specific nuclear protein and glutamate decarboxylase. We found that a column contains ∼2,200 INs (11.5% of ∼19,000 neurons), almost a factor of 2 less than previously estimated. The density of GABAergic neurons was inhomogeneous between layers, with peaks in the upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2 in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes were layer-specific. The “hot zones” of inhibition in L2 and L5A match the reported low stimulus-evoked spiking rates of excitatory neurons in these layers, suggesting that these inhibitory hot zones substantially suppress activity in the neocortex.}, web_url = {http://www.pnas.org/content/108/40/16807.full.pdf+html}, state = {published}, DOI = {10.1073/pnas.1113648108}, author = {Meyer HS; Schwarz D; Wimmer VC; Schmitt AC; Kerr JND{jkerr}; Sakmann B; Helmstaedter M} } @Article{ MittmannWCHSLDK2011, title = {Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo}, journal = {Nature Neuroscience}, year = {2011}, month = {8}, volume = {14}, number = {8}, pages = {1089-1093}, abstract = {Multiphoton imaging (MPI) is widely used for recording activity simultaneously from many neurons in superficial cortical layers in vivo. We combined regenerative amplification multiphoton microscopy (RAMM) with genetically encoded calcium indicators to extend MPI of neuronal population activity into layer 5 (L5) of adult mouse somatosensory cortex. We found that this approach could be used to record and quantify spontaneous and sensory-evoked activity in populations of L5 neuronal somata located as much as 800 μm below the pia. In addition, we found that RAMM could be used to simultaneously image activity from large (~80) populations of apical dendrites and follow these dendrites down to their somata of origin.}, web_url = {http://www.nature.com/neuro/journal/v14/n8/pdf/nn.2879.pdf}, state = {published}, DOI = {1038/nn.2879}, author = {Mittmann W{wmittmann}{Research Group Neural Population Imaging}; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Czubayko U{czubayko}{Research Group Neural Population Imaging}; Herb JT; Schaefer AT; Looger LL; Denk W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ 6936, title = {Timing is not everything: neuromodulation opens the STDP gate}, journal = {Frontiers in Synaptic Neuroscience}, year = {2010}, month = {10}, volume = {2}, number = {146}, pages = {1-14}, abstract = {Spike timing dependent plasticity (STDP) is a temporally specific extension of Hebbian associative plasticity that has tied together the timing of presynaptic inputs relative to the postsynaptic single spike. However, it is difficult to translate this mechanism to in vivo conditions where there is an abundance of presynaptic activity constantly impinging upon the dendritic tree as well as ongoing postsynaptic spiking activity that backpropagates along the dendrite. Theoretical studies have proposed that, in addition to this pre- and postsynaptic activity, a “third factor” would enable the association of specific inputs to specific outputs. Experimentally, the picture that is beginning to emerge, is that in addition to the precise timing of pre- and postsynaptic spikes, this third factor involves neuromodulators that have a distinctive influence on STDP rules. Specifically, neuromodulatory systems can influence STDP rules by acting via dopaminergic, noradrenergic, muscarinic, and nicotinic receptors. Neuromodulator actions can enable STDP induction or – by increasing or decreasing the threshold – can change the conditions for plasticity induction. Because some of the neuromodulators are also involved in reward, a link between STDP and reward-mediated learning is emerging. However, many outstanding questions concerning the relationship between neuromodulatory systems and STDP rules remain, that once solved, will help make the crucial link from timing-based synaptic plasticity rules to behaviorally based learning.}, web_url = {http://www.frontiersin.org/synaptic_neuroscience/10.3389/fnsyn.2010.00146/full}, state = {published}, DOI = {10.3389/fnsyn.2010.00146}, author = {Pawlak V{vpawlak}{Research Group Neural Population Imaging}; Wickens JR; Kirkwood A; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ 6666, title = {Chasing the cell assembly}, journal = {Current Opinion in Neurobiology}, year = {2010}, month = {6}, volume = {20}, number = {3}, pages = {296-305}, abstract = {Although we know enormous amounts of detailed information about the neurons that make up the cortex, placing this information back into the context of the behaving animal is a serious challenge. The functional cell assembly hypothesis first described by Hebb (The Organization of Behavior; a Neuropsychological Theory. New York: Wiley; 1949) aimed to provide a mechanistic explanation of how groups of neurons, acting together, form a percept. The vast number of neurons potentially involved make testing this hypothesis exceedingly difficult as neither the number nor locations of assembly members are known. Although increasing the number of neurons from which simultaneous recordings are made is of benefit, providing evidence for or against a hypothesis like Hebb‘s requires more than this. In this review, we aim to outline some recent technical advances, which may light the way in the chase for the functional cell assembly.}, web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6VS3-506S6JD-3-F&_cdi=6251&_user=29041&_pii=S0959438810000802&_orig=search&_coverDate=06%2F30%2F2010&_sk=999799996&view=c&wchp=dGLbVlb-zSkWA&md5=e5eff3b13f2048fe8aff86a11f133fab&ie=/sdarticle.pdf}, state = {published}, DOI = {10.1016/j.conb.2010.05.003}, author = {Wallace DJ{dhw}{Research Group Neural Population Imaging}; Kerr JN{jkerr}{Research Group Neural Population Imaging}} } @Article{ 6149, title = {Visually evoked activity in cortical cells imaged in freely moving animals}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2009}, month = {11}, volume = {106}, number = {46}, pages = {19557-19562}, abstract = {We describe a miniaturized head-mounted multiphoton microscope and its use for recording Ca2+ transients from the somata of layer 2/3 neurons in the visual cortex of awake, freely moving rats. Images contained up to 20 neurons and were stable enough to record continuously for >5 min per trial and 20 trials per imaging session, even as the animal was running at velocities of up to 0.6 m/s. Neuronal Ca2+ transients were readily detected, and responses to various static visual stimuli were observed during free movement on a running track. Neuronal activity was sparse and increased when the animal swept its gaze across a visual stimulus. Neurons showing preferential activation by specific stimuli were observed in freely moving animals. These results demonstrate that the multiphoton fiberscope is suitable for functional imaging in awake and freely moving animals.}, web_url = {http://www.pnas.org/content/early/2009/11/03/0903680106.full.pdf+html}, state = {published}, DOI = {10.1073/pnas.0903680106}, author = {Sawinski J{jsaw}{Research Group Neural Population Imaging}; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Grossmann S; Denk W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ 5350, title = {Automated Correction of Fast Motion Artifacts for Two-photon Imaging of Awake Animals}, journal = {Journal of Neuroscience Methods}, year = {2009}, month = {1}, volume = {176}, number = {1}, pages = {1-15}, abstract = {Two-photon imaging of bulk-loaded calcium dyes can record action potentials (APs) simultaneously from dozens of spatially resolved neurons in vivo. Extending this technique to awake animals, however, has remained technically challenging due to artifacts caused by brain motion. Since in two-photon excitation microscopes image pixels are captured sequentially by scanning a focused pulsed laser across small areas of interest within the brain, fast displacements of the imaged area can distort the image nonuniformly. If left uncorrected, brain motion in awake animals will cause artifactual fluorescence changes, masking the small functional fluorescence increases associated with AP discharge. We therefore present a procedure for detection and correction of both fast and slow displacements in two-photon imaging of awake animals. Our algorithm, based on the Lucas–Kanade framework, operates directly on the motion-distorted imaging data, requiring neither external signals such as heartbeat nor a distortion-free templa te image. Motion correction accuracy was tested in silico over a wide range of simplified and realistic displacement trajectories and for multiple levels of fluorescence noise. Accuracy was confirmed in vivo by comparing solutions obtained from red and green fluorophores imaged simultaneously. Finally, the accuracy of AP detection from motion-displaced bulk-loaded calcium imaging is evaluated with and without motion correction, and we conclude that accurate motion correction as achieved by this procedure is both necessary and sufficient for single AP detection in awake animals.}, web_url = {http://dx.doi.org/10.1016/j.jneumeth.2008.08.020}, state = {published}, DOI = {10.1016/j.jneumeth.2008.08.020}, author = {Greenberg DS{david}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ 5389, title = {Single-spike detection in vitro and in vivo with a genetic Ca2+ sensor}, journal = {Nature Methods}, year = {2008}, month = {8}, volume = {5}, number = {9}, pages = {797-804}, abstract = {Measurement of population activity with single-action-potential, single-neuron resolution is pivotal for understanding information representation and processing in the brain and how the brain‘s responses are altered by experience. Genetically encoded indicators of neuronal activity allow long-term, cell type–specific expression. Fluorescent Ca2+ indicator proteins (FCIPs), a main class of reporters of neural activity, initially suffered, in particular, from an inability to report single action potentials in vivo. Although suboptimal Ca2+-binding dynamics and Ca2+-induced fluorescence changes in FCIPs are important factors, low levels of expression also seem to play a role. Here we report that delivering D3cpv, an improved fluorescent resonance energy transfer–based FCIP, using a recombinant adeno-associated virus results in expression sufficient to detect the Ca2+ transients that accompany single action potentials. In upper-layer cortical neurons, we were able to detect transients associated with single action potentials firing at rates of}, web_url = {http://www.nature.com/nmeth/journal/v5/n9/pdf/nmeth.1242.pdf}, state = {published}, DOI = {10.1038/nmeth.1242}, author = {Wallace DJ{dhw}{Research Group Neural Population Imaging}; Borgloh SMZA; Astori S; Yang Y; Bausen M; K\"ugler S; Palmer AE; Tsien RY; Sprengel R; Kerr JND{jkerr}{Research Group Neural Population Imaging}; Denk W; Hasan MT} } @Article{ 5236, title = {Population imaging of ongoing neuronal activity in the visual cortex of awake rats}, journal = {Nature Neuroscience}, year = {2008}, month = {6}, volume = {11}, number = {7}, pages = {749-751}, abstract = {It is unclear how the complex spatiotemporal organization of ongoing cortical neuronal activity recorded in anesthetized animals relates to the awake animal. We therefore used two-photon population calcium imaging in awake and subsequently anesthetized rats to follow action potential firing in populations of neurons across brain states, and examined how single neurons contributed to population activity. Firing rates and spike bursting in awake rats were higher, and pair-wise correlations were lower, compared with anesthetized rats. Anesthesia modulated population-wide synchronization and the relationship between firing rate and correlation. Overall, brain activity during wakefulness cannot be inferred using anesthesia.}, web_url = {http://www.nature.com/neuro/journal/v11/n7/pdf/nn.2140.pdf}, state = {published}, DOI = {10.1038/nn.2140}, author = {Greenberg DS{david}{Research Group Neural Population Imaging}; Houweling AR; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ 5387, title = {Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity}, journal = {Journal of Neuroscience}, year = {2008}, month = {3}, volume = {28}, number = {10}, pages = {2435-2446}, web_url = {http://www.jneurosci.org/cgi/reprint/28/10/2435}, state = {published}, DOI = {10.1523/JNEUROSCI.4402-07.2008}, author = {Pawlak V{vpawlak}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ 5388, title = {Imaging in vivo: watching the brain in action}, journal = {Nature Reviews Neuroscience}, year = {2008}, month = {3}, volume = {9}, number = {3}, pages = {195-205}, abstract = {The appeal of in vivo cellular imaging to any neuroscientist is not hard to understand: it is almost impossible to isolate individual neurons while keeping them and their complex interactions with surrounding tissue intact. These interactions lead to the complex network dynamics that underlie neural computation which, in turn, forms the basis of cognition, perception and consciousness. In vivo imaging allows the study of both form and function in reasonably intact preparations, often with subcellular spatial resolution, a time resolution of milliseconds and a purview of months. Recently, the limits of what can be achieved in vivo have been pushed into terrain that was previously only accessible in vitro, due to advances in both physical-imaging technology and the design of molecular contrast agents.}, web_url = {http://www.nature.com/nrn/journal/v9/n3/pdf/nrn2338.pdf}, state = {published}, DOI = {10.1038/nrn2338}, author = {Kerr JND{jkerr}{Research Group Neural Population Imaging}; Denk W} } @Article{ 5213, title = {Spatial Organization of Neuronal Population Responses in Layer 2/3 of Rat Barrel Cortex}, journal = {Journal of Neuroscience}, year = {2007}, month = {11}, volume = {27}, number = {48}, pages = {13316-13328}, abstract = {Individual pyramidal neurons of neocortex show sparse and variable responses to sensory stimuli in vivo. It has remained unclear how this variability extends to population responses on a trial-to-trial basis. Here, we characterized single-neuron and population responses to whisker stimulation in layer 2/3 (L2/3) of identified columns in rat barrel cortex using in vivo two-photon calcium imaging. Optical detection of single action potentials from evoked calcium transients revealed low spontaneous firing rates (0.25 Hz), variable response probabilities (range, 0–0.5; mean, 0.2 inside barrel column), and weak angular tuning of L2/3 neurons. On average, both the single-neuron response probability and the percentage of the local population activated were higher in the barrel column than above septa or in neighboring columns. Within the barrel column, mean response probability was highest in the center (0.4) and declined toward the barrel border. Neuronal pairs showed correlations in both spontaneous and sensory-evoked activity that depended on the location of the neurons. Correlation decreased with increasing distance between neurons and, for neuronal pairs the same distance apart, with distance of the pair from the barrel column center. Although neurons are therefore not activated independently from each other, we did not observe precisely repeating spatial activation patterns. Instead, population responses showed large trial-to-trial variability. Nevertheless, the accuracy of decoding stimulus onset times from local population activity increased with population size and depended on anatomical location. We conclude that, despite their sparseness and variability, L2/3 population responses show a clear spatial organization on the columnar scale.}, web_url = {http://www.jneurosci.org/cgi/reprint/27/48/13316}, state = {published}, DOI = {10.1523/JNEUROSCI.2210-07.2007}, author = {Kerr JND{jkerr}; de Kock CPJ; Greenberg DS{david}; Bruno RM; Sakman B; Helmchen F} } @Article{ 5212, title = {Imaging input and output of neocortical networks in vivo}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2005}, month = {9}, volume = {102}, number = {39}, pages = {14063-14068}, abstract = {Neural activity manifests itself as complex spatiotemporal activation patterns in cell populations. Even for local neural circuits, a comprehensive description of network activity has been impossible so far. Here we demonstrate that two-photon calcium imaging of bulk-labeled tissue permits dissection of local input and output activities in rat neocortex in vivo. Besides astroglial and neuronal calcium transients, we found spontaneous calcium signals in the neuropil that were tightly correlated to the electrocorticogram. This optical encephalogram (OEG) is shown to represent bulk calcium signals in axonal structures, thus providing a measure of local input activity. Simultaneously, output activity in local neuronal populations could be derived from action potential-evoked calcium transients with single-spike resolution. By using these OEG and spike activity measures, we characterized spontaneous activity during cortical Up states. We found that (i) spiking activity is sparse (}, web_url = {http://www.pnas.org/content/102/39/14063.full.pdf+html}, state = {published}, DOI = {10.1073/pnas.0506029102}, author = {Kerr JND{jkerr}; Greenberg D{david}; Helmchen F} } @Article{ GobelKNH2004, title = {Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective}, journal = {Optics Letters}, year = {2004}, month = {11}, volume = {29}, number = {21}, pages = {2521-2523}, abstract = {We present a miniature, flexible two-photon microscope consisting of a fused coherent optical fiber bundle with 30,000 cores and a gradient-index lens objective. The laser focus of a standard two-photon laser-scanning microscope was scanned over the entrance surface of the fiber bundle, resulting in sequential coupling into individual cores. Fluorescent light was detected through the fiber bundle. Micrometer-sized fluorescent beads and pollen grains were readily resolved. In addition, fluorescently labeled blood vessels were imaged through the fiber bundle in rat brain in vivo.}, web_url = {http://www.opticsinfobase.org/ol/abstract.cfm?uri=ol-29-21-2521}, state = {published}, DOI = {10.1364/OL.29.002521}, author = {G\"obel W; Kerr JND{jkerr}; Nimmerjahn A; Helmchen F} } @Article{ NimmerjahnKKH2004, title = {Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo}, journal = {Nature Methods}, year = {2004}, month = {10}, volume = {1}, number = {1}, pages = {31-37}, abstract = {Glial cells have been identified as key signaling components in the brain; however, methods to investigate their structure and function in vivo have been lacking. Here, we describe a new, highly selective approach for labeling astrocytes in intact rodent neocortex that allows in vivo imaging using two-photon microscopy. The red fluorescent dye sulforhodamine 101 (SR101) was specifically taken up by protoplasmic astrocytes after brief exposure to the brain surface. Specificity was confirmed by immunohistochemistry. In addition, SR101 labeled enhanced green fluorescent protein (EGFP)-expressing astrocytes but not microglial cells in transgenic mice. We used SR101 labeling to quantify morphological characteristics of astrocytes and to visualize their close association with the cortical microvasculature. Furthermore, by combining this method with calcium indicator loading of cell populations, we demonstrated distinct calcium dynamics in astroglial and neuronal networks. We expect SR101 staining to become a principal tool for investigating astroglia in vivo.}, web_url = {http://www.nature.com/nmeth/journal/v1/n1/pdf/nmeth706.pdf}, state = {published}, DOI = {10.1038/nmeth706}, author = {Nimmerjahn A; Kirchhoff F; Kerr JND{jkerr}; Helmchen F} } @Article{ KerrP2004, title = {Action potential timing determines dendritic calcium during striatal up-states}, journal = {Journal of Neuroscience}, year = {2004}, month = {1}, volume = {24}, number = {4}, pages = {877-985}, abstract = {Up-states represent a key feature of synaptic integration in cortex and striatum that involves activation of many synaptic inputs. In the striatum, the sparse firing and tight control of action potential timing is in contrast to the large intracellular membrane potential depolarizations observed during the up-state. One hallmark of striatal spiny projection neurons is the delay to action potential generation in both up-states and suprathreshold depolarization by somatic current injection. By studying somatic and dendritic intracellular calcium ([Ca2+]i) transients during spontaneous up-states in cortex–striatum–substantia nigra organotypic cultures, we show that the delay between up-state onset and action potential generation determines dendritic peak [Ca2+]i. Peak [Ca2+]i from single action potentials reached maximum values when action potentials were close to up-state onset and sharply decayed to near subthreshold up-state [Ca2+] levels as a function of time (τ = 47 ± 26 msec for tertiary dendrite). Similarly, a precisely timed action potential elicited during subthreshold up-states through somatic current injection established that the delay between up-state onset and action potential generation is the critical variable that controls peak [Ca2+]i. Blocking NMDA channels internally with high intracellular Mg2+ ([Mg2+]i) (10 mm) abolished the dependency of peak [Ca2+]i on action potential timing during spontaneous up-states. Finally, high [Mg2+]i specifically blocked [Ca2+]i transients that resulted from local NMDA application in conjunction with backpropagating action potentials. We conclude that precisely timed, single action potentials during striatal up-states control peak dendritic calcium levels. We suggest that this mechanism might play an important role in synaptic plasticity of the corticostriatal pathway.}, web_url = {http://www.jneurosci.org/content/24/4/877.full.pdf+html}, state = {published}, DOI = {10.1523/​JNEUROSCI.4475-03.2004}, author = {Kerr JND{jkerr}; Plenz D} } @Article{ KerrP2002, title = {Dendritic calcium encodes striatal neuron output during up-states}, journal = {Journal of Neuroscience}, year = {2002}, month = {3}, volume = {22}, number = {5}, pages = {1499-1512}, abstract = {Striatal spiny projection neurons control basal ganglia outputs via action potential bursts conveyed to the globus pallidus and substantia nigra. Accordingly, burst activity in these neurons contributes importantly to basal ganglia function and dysfunction. These bursts are driven by multiple corticostriatal inputs that depolarize spiny projection neurons from their resting potential of approximately −85 mV, which is the down-state, to a subthreshold up-state of −55 mV. To understand dendritic processing of bursts during up-states, changes in intracellular calcium concentration ([Ca2+]i) were measured in striatal spiny projection neurons from cortex–striatum–substantia nigra organotypic cultures grown for 5–6 weeks using somatic whole-cell patch recording and Fura-2. During up-states, [Ca2+]i transients at soma and primary, secondary, and tertiary dendrites were highly correlated with burst strength (i.e., the number of spontaneous action potentials). During down-states, the action potentials evoked by somatic current pulses elicited [Ca2+]i transients in higher-order dendrites that were also correlated with burst strength. Evoked bursts during up-states increased dendritic [Ca2+]i transients supralinearly by >200% compared with the down-state. In the presence of tetrodotoxin, burst-like voltage commands failed to elicit [Ca2+]i transients at higher-order dendrites. Thus, dendritic [Ca2+]itransients in spiny projection neurons encode somatic bursts supralinearly during up-states through active propagation of action potentials along dendrites. We suggest that this conveys information about the contribution of a spiny projection neuron to a basal ganglia output specifically back to the corticostriatal synapses involved in generating these outputs.}, web_url = {http://www.jneurosci.org/content/22/5/1499.long}, state = {published}, author = {Kerr JND{jkerr}; Plenz D} } @Article{ KerrW2001, title = {Dopamine D-1/D-5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro}, journal = {Journal of Neurophysiology}, year = {2001}, month = {1}, volume = {95}, number = {1}, pages = {117-124}, abstract = {Dopamine and glutamate are key neurotransmitters involved in learning and memory mechanisms of the brain. These two neurotransmitter systems converge on nerve cells in the neostriatum. Dopamine modulation of activity-dependent plasticity at glutamatergic corticostriatal synapses has been proposed as a cellular mechanism for learning in the neostriatum. The present research investigated the role of specific subtypes of dopamine receptors in long-term potentiation (LTP) in the corticostriatal pathway, using intracellular recording from striatal neurons in a corticostriatal slice preparation. In agreement with previous reports, LTP could be induced reliably under Mg2+-free conditions. This Mg2+-free LTP was blocked by dopamine depletion and by the dopamine D-1/D-5 receptor antagonist SCH 23390 but was not blocked by the dopamine D-2 receptor antagonist remoxipride or the GABAA antagonist picrotoxin. In dopamine-depleted slices, the ability to induce LTP could be restored by bath application of the dopamine D-1/D-5 receptor agonist, SKF 38393. These results show that activation of dopamine D-1/D-5 receptors by either endogenous dopamine or exogenous dopamine agonists is a requirement for the induction of LTP in the corticostriatal pathway. These findings have significance for current understanding of learning and memory mechanisms of the neostriatum and for theoretical understanding of the mechanism of action of drugs used in the treatment of psychotic illnesses and Parkinson's disease.}, web_url = {http://jn.physiology.org/content/85/1/117.long}, state = {published}, author = {Kerr JND{jkerr}; Wickens JR} } @Inproceedings{ WallaceK2016, title = {Chasing the Cortical Assembly}, year = {2012}, month = {10}, day = {12}, pages = {41-50}, abstract = {Why is the cortex so difficult to understand? Although we know enormous amounts of detailed information about the neurons that make up the cortex, placing this information back into context of the behaving animal is a serious challenge. In this chapter, we aim to outline some recent technical advances that may light the way toward the chase for the functional ensemble. We summarize the progress that has been made using optical recording approaches with a view to what can be expected in the near future, given the recent technological advances. The modeling and theoretical arguments surrounding neuronal ensembles have been described in great detail previously (Palm, 1982; Braitenberg, 1978; Gerstein et al., 1989; Harris, 2005; Mountcastle, 1997, 2003; Wickens and Miller, 1997), so we will not review them here.}, web_url = {https://www.sfn.org/Careers-and-Training/Career-Tools-and-Resources/Short-Courses/2012-Short-Course-II}, event_name = {Society for Neuroscience: 2012 Short Course II MRI and Advanced Imaging in Animals and Humans}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Wallace DJ{dhw}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Inbook{ 6937, title = {Imaging Neuronal Population Activity in Awake and Anesthetized Rodents}, year = {2011}, month = {5}, pages = {839-850}, web_url = {http://www.cshlpress.com/default.tpl?cart=132033207747169484&fromlink=T&linkaction=full&linksortby=oop_title&--eqSKUdatarq=881}, editor = {Helmchen, F. , A. Konnerth, R. Yuste}, publisher = {Cold Spring Harbour Laboratory Press}, address = {Cold Spring Harbor, NY, USA}, booktitle = {Imaging in Neuroscience: A Laboratory Manual}, state = {published}, ISBN = {978-0-87969-938-3}, author = {Greenberg DS{david}{Research Group Neural Population Imaging}; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Inbook{ 6938, title = {Miniaturization of Two-Photon Microscopy for Imaging in Freely Moving Animals}, year = {2011}, month = {5}, pages = {851-862}, web_url = {http://www.cshlpress.com/default.tpl?cart=132033207747169484&fromlink=T&linkaction=full&linksortby=oop_title&--eqSKUdatarq=881}, editor = {Helmchen, F. , A. Konnerth, R. Yuste}, publisher = {Cold Spring Harbour Laboratory Press}, address = {Cold Spring Harbor, NY, USA}, booktitle = {Imaging in Neuroscience: A Laboratory Manual}, state = {published}, ISBN = {978-0-879699-38-3}, author = {Helmchen F; Denk W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ CzubaykoBNOMK2015, title = {Anatomical basis of spiking correlation in upper layers of somatosensory cortex}, year = {2015}, month = {10}, day = {18}, volume = {45}, number = {240.25}, abstract = {In neuronal populations of the sensory cortex, stimulus responses are shaped by the cortical architecture on anatomical scales from tens of microns to millimeters. In particular, in L2/3 rodent vibrissal cortex we previously observed that whisker deflection evokes pairwise correlations that decrease both with distance between neurons and distance to the center of the whisker-associated column (Kerr, de Kock, Greenberg, Bruno, Sakmann, and Helmchen. (2007). J. Neurosci. 27: 13316-28). One possible explanation for this finding is that these correlations arise from anatomically structured common inputs. L4 spiny stellate (SS) cells send vertical axon fibers to L2/3 that are confined within the borders of the whisker-associated column and neuronal pairs closer together could exhibit greater dendritic overlap. Therefore, for pairs closer to the column center more of this overlap will intersect with SS projections. We tested this hypothesis using 2-photon targeted patching of L2/3 pyramidal pairs in anaesthetized rats to record sub- and suprathreshold stimulus responses followed by anatomic reconstruction of the neurons and barrel field. We found a positive and statistically significant association between correlated AP firing and dendritic overlay inside the whisker-associated column. This effect was strongest for suprathreshold activity evoked shortly after whisker deflection (~20 ms), and decayed rapidly thereafter. It was also robust with respect to the voxel size, determined by the L4 axon reconstructions, used to quantify dendritic overlap. No relationship was detectable for offset responses or spontaneous activity. These results support the notion that the spatially structured correlations observed for short-latency stimulus-evoked spiking arise from anatomically structured feed-forward projections.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Czubayko U{czubayko}; Bassetto G{gbassetto}; Narayanan RT{rnarayanan}; Oberlaender M{moberlaender}; Macke JH{jakob}; Kerr JND{jkerr}} } @Poster{ RullaNMWSK2015, title = {Two-photon imaging of neuronal populations in the primary visual cortex representation of the overhead visual field}, year = {2015}, month = {10}, day = {18}, volume = {45}, number = {232.10}, abstract = {Rodents have a large binocular field of view that extends from the snout to over the animals head. Recent experiments have shown that rodents have a strong, innate, evasive behavior evoked exclusively by stimuli presented above them. However, little is known about the functional properties of cortical neurons that represent the overhead visual field. Here we describe a method for allowing direct optical recording from populations of neurons representing the overhead visual field. Firstly, the conventional microscope objective has been replaced with a periscope coupled to a miniature objective to facilitate placement of a stimulus monitor above the rat’s head. Secondly, we developed a method for presentation of visual stimuli on the OLED display of a tablet running the Android OS, and a camera-based method for calibrating the position of the stimulus display in relation to the animals head. Using this setup, we recorded in rats the activity of neurons in the representation of the overhead visual field of the primary visual cortex in response to a range of stimuli. Neurons were labeled with the calcium indicator OGB-1 with counterstaining of astrocytes using sulforhodamine 101. Stimuli were either an expanding or contracting looming dot, or a moving dot that moved at constant speed along multiple trajectories to cover all positions within the display. In both stimulus types, differing sets of foreground/background luminance were used. Preliminary results show that 19% of the neurons responded with clear and reproducible transients to the looming dot stimulus, and 30% were responsive to moving dot stimuli. The response profiles of neurons to different stimulus types and parameters were further analyzed in detail and compared between cortical areas and receptive field properties established for this cortical region.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Rulla S{rulla}; Ng B{benedict}; Macke J{jakob}; Wallace D{dhw}; Sawinski J{jsaw}; Kerr J{jkerr}} } @Poster{ EggerSDNdKO2015, title = {Reverse Engineering the 3D Structure and In Vivo Function of Rat Vibrissal Cortex}, year = {2014}, month = {6}, web_url = {http://brain.korea.ac.kr/bce2014/?m=program}, event_name = {6th International Conference on Brain and Cognitive Engineering (BCE 2014)}, event_place = {Tübingen, Germany}, state = {published}, author = {Egger R{regger}; Schmitt AC{aschmitt}{Research Group Neural Population Imaging}; Dercksen VJ; Narayanan RT{rnarayanan}; de Kock CPJ; Kerr J{jkerr}{Research Group Neural Population Imaging}; Oberlaender M{moberlaender}} } @Poster{ EggerSDdKO2013, title = {Reverse-engineering sensory-evoked signal flow in rat barrel cortex}, year = {2013}, month = {11}, day = {9}, volume = {43}, number = {71.19}, abstract = {We present a novel reverse-engineering approach that allows investigating sensory-evoked signal flow through individual neurons within the context of their surrounding neural networks. To do so, spontaneous and sensory-evoked activity is recorded from individual neurons in vivo. In addition, the complete 3D dendrite and axon projection patterns of these neurons are reconstructed and registered into an anatomically realistic model of rat barrel cortex. This model allows estimating the number and cell type-specific subcellular distribution of synapses on these neurons. Next, the neurons are “wired” into the network by connecting the synapses to presynaptic neurons based on cell type-specific connection probabilities. The number of functional synapses on this neuron is determined by including measurements of cell type-specific ongoing and sensory-evoked spiking probabilities for all presynaptic cell types. Finally, this neuron is turned into a compartmental model and constrained by comparing model responses to ongoing and sensory-evoked synaptic inputs to in vivo measured responses. For the first time, this allows investigating in vivo measured sensory-evoked responses of single neurons in anatomically realistic computer models, complementing previous biophysically detailed models of single neurons based on in vitro experiments. To investigate the mechanistic principles underlying sensory responses in different cell types, we use a Monte Carlo method for sampling the parameter space of the network-embedded neuron model. For example, by varying the functional connectivity or timing of sensory input, we identify model configurations that match the in vivo observed responses of these neurons. As a first demonstration of the feasibility of this approach, we investigate sensory-evoked responses in two different pathways in rat barrel cortex. First, based on axonal innervation, we find that Layer 1 inhibitory interneurons may form synapses with the apical tuft dendrites of Layer 2 (L2) neurons. Our model and experiments show that these inhibitory synapses may serve to reduce the trial-to-trial variability of the sensory-evoked PSP in L2 neurons located in surrounding columns after deflection of the principal whisker. Second, we investigate thalamocortical activation of Layer 4 (L4) neurons after passive whisker touch. Our model shows that this cell type is preferentially activated by synchronous thalamic input from VPM and ongoing intracortical activity, which together create an NMDA receptor-mediated global depolarization that leads to spiking output of this cell type.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Egger R{regger}; Schmitt AC{aschmitt}{Research Group Neural Population Imaging}; Dercksen VJ; de Kock CPJ; Kerr J{jkerr}{Research Group Neural Population Imaging}; Oberlaender M{moberlaender}} } @Poster{ EggerSDNdKO2013, title = {Reverse-engineering sensory-evoked signal flow in rat barrel cortex}, year = {2013}, month = {11}, event_name = {26th Annual Barrels Meeting (Barrels XXVI)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Egger R{regger}; Schmitt AC{aschmitt}{Research Group Neural Population Imaging}; Dercksen VJ; Narayanan R{rnarayanan}; de Kock CPJ; Kerr J{jkerr}{Research Group Neural Population Imaging}; Oberlaender M{moberlaender}} } @Poster{ EggerSdKO2013, title = {Reverse-engineering sensory-evoked signal flow in rat barrel cortex}, year = {2013}, month = {9}, pages = {171}, abstract = {We present a novel reverse-engineering approach that allows investigating sensory-evoked signal flow through individual neurons within the context of their surrounding neural networks. To do so, spontaneous and sensory-evoked activity is recorded from individual neurons in vivo. In addition, the complete 3D dendrite and axon projection patterns of these neurons are reconstructed and registered into an anatomically realistic model of rat barrel cortex. This model allows estimating the number and cell type-specific subcellular distribution of synapses on these neurons. Next, the neurons are “wired” into the network by connecting the synapses to presynaptic neurons based on cell type-specific connection probabilities. The number of functional synapses on this neuron is determined by including measurements of cell type-specific ongoing and sensory-evoked spiking probabilities for all presynaptic cell types. Finally, this neuron is turned into a compartmental model and constrained by comparing model responses to ongoing and sensory-evoked synaptic inputs to in vivo measured responses. For the first time, this allows investigating in vivo measured sensory-evoked responses of single neurons in anatomically realistic computer models, complementing previous biophysically detailed models of single neurons based on in vitro experiments. To investigate the mechanistic principles underlying sensory responses in different cell types, we use a Monte Carlo method for sampling the parameter space of the network-embedded neuron model. For example, by varying the functional connectivity or timing of sensory input, we identify model configurations that match the in vivo observed responses of these neurons. As a first demonstration of the feasibility of this approach, we investigate sensory-evoked responses in two different pathways in rat barrel cortex.}, web_url = {https://portal.g-node.org/abstracts/bc13/#/doi/nncn.bc2013.0178}, event_name = {Bernstein Conference 2013}, event_place = {Tübingen, Germany}, state = {published}, DOI = {10.12751/nncn.bc2013.0178}, author = {Egger R{regger}; Schmitt AC{aschmitt}{Research Group Neural Population Imaging}; de Kock CPJ; Kerr J{jkerr}{Research Group Neural Population Imaging}; Oberlaender M{moberlaender}} } @Poster{ EggerNMGSKdO2013, title = {Beyond barrel columns: Structural organization principles of neural circuits in rat vibrissal cortex}, year = {2013}, month = {4}, web_url = {http://janelia.org/conferences-events/overview}, event_name = {HHMI Janelia Farm Conference: The Neural Basis of Vibrissa-Based Tactile Sensation}, event_place = {Ashburn, VA, USA}, state = {published}, author = {Egger R{regger}; Narayanan R{rnarayanan}; Meyer HS; Guest JM; Schmitt AC{aschmitt}{Research Group Neural Population Imaging}; Kerr J{jkerr}{Research Group Neural Population Imaging}; de Kock CPJ; Oberlaender M{moberlaender}} } @Poster{ SawinskiGWK2012, title = {Combining ocular videography and 2-photon imaging in freely moving rats}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {569.29}, abstract = {Accurately recording eye movements is essential to understanding how an animal moves its eyes to establish vision. Rodents are a commonly used as a model for the mammalian visual system, but it is not known how they move their eyes during free movement. We describe here a custom-built ocular videography system light enough to be carried_in combination with a head-mount two-photon microscope (Sawinski et al., 2009)on the head of a freely moving rat. Each camera, complete with mounting arm and infrared (IR) illumination weighs 1.8 g, with outer dimensions of the camera about 2.5×1×1 cm³. Rats comfortably carry 2 cameras, one recording the movements of each eye. The off-the-shelf monochrome camera chips (Aptina) are capable of recording 752×480 pixel images at a maximum frame rate of 60 Hz, and have a wide wavelength range which allows IR illumination. Using a 45° IR reflector that is transparent to visible light allows the cameras to be positioned in a way that minimizes disturbance to the animal’s visual field. The optics consist of a plano-convex lens (focal length f=9 mm) and a visible-light reflector. The lens is mounted in reverse orientation favoring a more planar image plane. The image size is 1.3×0.9 cm² at a working distance of about 1 cm. Inbuilt illumination from an IR LED (850nm) provides consistent image quality during normal exploratory behaviors and jumping. Image quality and resolution is good enough to identify the fine detail of the edge of the iris, which can be used for the detection of ocular torsion (rotation of the eye around the optical axis). Cabling is minimal, as the camera chip can be controlled with a two-wire serial interface and is able to transmit image data over a twisted pair using low-voltage differential signaling (LVDS). To reduce rotational stiffness we have built 2 m long custom cables by twisting enameled 50 µm dia. copper wires. While the wire resistance is less critical for LVDS signaling (even though the impedance is lower than required due to small wire separation) the voltage-level-wise sensitive two-wire serial communication required galvanic separation of the ground connection of the mobile cameras power supply and the external signal decoding board. The signals are then decoded on a custom-built decoding board using a standard LVDS deserializer (12bit) and an additional two-wire serial bus buffer. Signals are then transmitted via a USB interface. In combination with the miniature two-photon microscope, the eye-cameras are deployed in combination with a fully optical head-orientation detection system consisting of 6 IR LEDs mounted on the animal’s head with the miniaturized cameras, and a set of 4 external overhead cameras.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=c2acba4a-3c88-400b-8cf8-710fdf9d735b&cKey=d1e3e411-5ec5-471e-ba5b-08c8049a76fa&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Sawinski J{jsaw}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Poster{ WallaceSGNRK2012, title = {Eye movements in rats maintain an overhead binocular field at the expense of binocular fusion}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {569.28}, abstract = {How much does an unrestrained rat move its eyes, and what are the characteristics of these movements? Though many elements of rat vision have been well studied, such as their perception of depth and color, their visual acuity, and the physiology of neurons in the retina, thalamus and visual cortex, this essential element in understanding their visual sense has not been studied to date in unrestrained animals. To study this aspect of rat vision, we recorded eye movements in freely moving rats using a custom-built miniaturized ocular-videography system. A large fraction of the movements were found to be disconjugate and not consistent with the maintenance of a common point of fixation for both eyes, with the line of gaze of the two eyes regularly pointing in substantially different directions. Saccade-like conjugate movements, while forming the majority of movements seen in head-restrained animals, were only a small fraction of the movements observed in unrestrained animals. The asymmetrical movements of the two eyes implies substantial variability in the correspondence of the left and right eye images, and this, together with the lack of a common point of fixation for both eyes, precludes binocular fusion (fusion of left and right eye images into a single visual percept) and stereoscopic binocular vision using the mechanism described for other animals such as cats and primates. Movements of the two eyes were continuous while the animal was moving, but reduced to near stationary when the animal stopped moving its head, reflecting the strong influence of the vestibulo-ocular system in the rat. Horizontal movements of the eyes (movements in the rostral-caudal axis) were strongly related to head pitch, nose up pitch resulting in convergent movements of the two eyes and nose down pitch divergent movements. Vertical movements were strongly related to head roll, with roll to the right resulting in dorsally-directed movement of the right eye and ventrally directed movement of the left. Combined analysis of eye and head movements showed that the eye movements stabilize the animal’s horizon by moving and rotating the eyes in a way that counteracts the perturbations of the orientation of the horizontal axis of the retina caused by movements of the head. In addition, these movements also keep the visual fields of the two eyes strongly overlapping above the animal the vast majority of the time, which may be of substantial evolutionary benefit for a small ground dwelling animal. We suggest that the selective pressure on the rat has led to its visual system being rather more specialized to maximize overhead surveillance at the expense of binocular fusion and stereoscopic vision.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=c2acba4a-3c88-400b-8cf8-710fdf9d735b&cKey=59f3b1cb-6e31-4c11-9b39-58d10b46cc64&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Wallace DJ{dhw}{Research Group Neural Population Imaging}; Sawinski J{jsaw}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Notaro G{gnotaro}; Rulla S{rulla}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ GreenbergWSNRK2012, title = {Optical tracking of head movements, eye movements and ocular torsion incorporated into a miniaturized two-photon microscope}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {569.27}, abstract = {The miniaturized two photon (2P) microscope or ‘fiberscope’ allows imaging during free movement, requiring continuous tracking of the head and eyes to determine visual input. We developed a 2P-compatible, all-optical system for head and eye tracking in rodents. Head tracking with 6 DOF employed infrared LEDs mounted on the microscope and imaged by multiple overhead cameras, while miniaturized camera systems with specialized, custom-built optics and electronics were used to image the eyes (see accompanying poster for details). Calibration procedures based on the Tsai camera model realistically incorporated radial lens distortion, and for custom-built camera systems decentering and thin-prism distortions as well. To detect eye movements, we directly compared 3D geometric models of the eye and pupil to each observed image, minimizing an objective function over eye rotation angles and pupil dilation radii. We found that this approach, which detected the 2D pupil boundary and 3D eye rotation simultaneously in a single step, was more robust than previous methods with an intermediate stage of 2D feature detection, allowing our system to operate effectively at lower contrast. Since the pupil-iris boundary deviated slightly from a perfect circle, with an uneven, crenellated appearance on a fine spatial scale, we also detected ocular torsion by measuring rotation of this rough boundary through 3D space. The eye tracker was self-calibrating in that animals were not required to fixate a presented target, aiding the use of this system in rodents where such training is impossible. Finally, based on the appearance of the eyeball-eyelid boundary we defined anatomically based coordinate axes and baseline pupil positions that were consistent across animals, even when the location and orientation of eye tracking cameras varied. Together, these tracking systems and analysis methods allowed stimulus presentation monitors and other environmental features to be mapped continuously onto each pupil plane, and gaze vectors for each eye to be projected into the animal’s environment.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=c2acba4a-3c88-400b-8cf8-710fdf9d735b&cKey=d565ef28-d831-42fa-b72e-f0a377971f43&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Greenberg DS{david}{Research Group Neural Population Imaging}; Wallace D{dhw}{Research Group Neural Population Imaging}; Sawinski J{jsaw}{Research Group Neural Population Imaging}; Notaro G{gnotaro}; Rulla S{rulla}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ PawlakGSGK2012, title = {Spike-timing dependent plasticity changes responses of cortical neurons from sub- to supra-threshold in vivo}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {572.01}, abstract = {A broad range of visual stimuli generate synaptic input to visual cortex neurons, whereas only a small selection of stimuli generates action potential output from the neuron, that informs downstream targets of the sensory event - but whether plasticity rules can predictably change the spiking response of a neuron by changing a subthreshold response into a suprathreshold response, although proposed, is unclear. Here, we show that a brief spike-timing dependent plasticity (STDP) protocol consisting of close timing of postsynaptic action potentials (APs) and presynaptic inputs derived from visual stimulation can convert subthreshold responses into suprathreshold responses and restructure the neuron's suprathreshold receptive field. This reorganization of spiking responses was paralleled by a change in the time course of the subthreshold voltages and was abolished when muscarinic acetylcholine receptors were blocked. Computational simulations, based on in vitro STDP data, could reproduce the subthreshold membrane potential changes reported here, only when temporal jitter, based on in vivo data, was included during pairing at the presynaptic input stage. Together this shows that timing based plasticity rules, using 10’s postsynaptic spikes, has a functional impact on the spiking response patterns of sensory neurons in vivo by changing suprathreshold tuning properties of the visual cortex neurons.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=080529e4-b28c-45c0-9c78-317a4cb68dcb&cKey=3d077755-c40b-4ec1-b4e7-b44858c81c44&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Pawlak V{vpawlak}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Sprekeler H; Gerstner W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ NaumannKRB2011, title = {Translaminar imaging of calcium signals evoked by sensory stimuli in Etruscan shrew somatosensory cortex}, year = {2011}, month = {11}, volume = {41}, number = {704.08}, abstract = {The Etruscan shrew, Suncus etruscus, is the smallest terrestrial mammal with a body weight of ~ 2 g and a body length of ~ 4 cm. The small size of the Etruscan shrew’s brain offers particular advantages for imaging, as the entire cortical sheet as well as somatosensory cortex are on average less than 500 µm thick. Here we show that in this animal two photon imaging allows to visualize all cortical layers, which is typically difficult to do in rodents or other mammals. Although much is known about the activity of individual cells, the pattern of activity across an entire column during sensory stimulation is less well understood. Using bulk loading of calcium indicators in the somatosensory cortex of anaesthetized shrews, we aim to describe the cellular activity of populations of neurons in somatosensory cortex across different layers. We characterize single-neuron and multi-neuron responses to whisker stimuli using optically recorded calcium transients. Our preliminary data indicate that responses are heterogeneous in Etruscan shrew cortex. Much like observed previously in rodent somatosensory cortex there is little spontaneous activity and even powerful stimuli (air puffs) evoke only sparse responses.}, web_url = {http://www.sfn.org/am2012/}, event_name = {41st Annual Meeting of the Society for Neuroscience (Neuroscience 2011)}, event_place = {Washington, DC, USA}, state = {published}, author = {Naumann RK; Kerr JND{jkerr}{Research Group Neural Population Imaging}; Roth-Alpermann C; Brecht M} } @Poster{ MullerBierlPKUU2012, title = {A realistic vascular model for BOLD signal up to 16.4 T}, year = {2010}, month = {5}, day = {4}, volume = {2010}, number = {1129}, abstract = {The blood oxygenation level-dependent (BOLD) signal using functional magnetic resonance imaging (fMRI) is currently the most popular imaging method to study brain function non-invasively. The sensitivity of the BOLD signal to different types of MRI sequences and vessel sizes is currently under investigation [1]. Gradient echo (GRE) sequences are known to be sensitive to larger vessels (venules and veins), whereas spin-echo (SE) sequences are generally more sensitive to smaller vessels (venules and capillaries), especially at high magnetic field strength [2, 3]. However, the widely used single vessel model is only an approximation to the realistic vascular distribution. Realistic vascular models have been proposed by Marques and Bowtell [4] and, recently, by Chen et al.[5]. We herein present a realistic vascular model (RVM) where diffusion is accounted for by a Monte-Carlo random walk.}, file_url = {fileadmin/user_upload/files/publications/ISMRM-2010-1129.PDF}, web_url = {http://www.ismrm.org/10/}, event_name = {ISMRM-ESMRMB Joint Annual Meeting 2010}, event_place = {Stockholm, Sweden}, state = {published}, author = {M\"uller-Bierl AM{mrbierl}{Department High-Field Magnetic Resonance}; Pawlak V{vpawlak}{Research Group Neural Population Imaging}; Kerr J{jkerr}{Research Group Neural Population Imaging}; Ugurbil K; Uludag K{kuludag}{Department High-Field Magnetic Resonance}} } @Poster{ SchmittWSK2009, title = {Sensory evoked responses of interneurons in layers 1 and 2 of rat somatosensory cortex in vivo}, year = {2009}, month = {10}, volume = {39}, number = {364.9}, abstract = {Interneurons (INs) are thought to play a large role in the shaping of neuronal activity during sensory input as well as during spontaneous activity. Despite this important function, almost all of electrophysiological recordings have been performed in vitro and functional data has mainly stemmed from paired recordings in the acute slice. Using 2-photon microscopy in combination with whole-cell patch-clamp recordings we were able to reliably target INs in layers 1 and 2 of the rat somatosensory cortex, in vivo. Intrinsic optical signal imaging was used to find the cortical column primary activated by a particular whisker. Post hoc staining and reconstruction was used to confirm the cell type and the position of the recorded neurons. We recorded from both INs (n = 30) and pyramidal neurons (PNs) (n = 15) in layers 1 and 2 of barrel cortex (average depth +/- SD: -62 +/- 35 μm and 144 +/- 50 μm). INs showed significantly higher rates of spontaneously occurring action potentials than PNs (1.12 +/- 0.06 Hz vs. 0.25 +/- 0.08 Hz, for INs (n=20) and PNs (n=15); p<0.0015) while the frequency of Up states was the same in both cell types (1.92 +/-0.09 Hz and 1.97 +/-0.09 Hz). Sensory stimulation caused subthreshold membrane potential deflections in all neurons recorded. The latency from whisker deflection onset to 10% EPSP amplitude was 8.89+/-0.33ms for INs and 10.02 +/- 0.58ms for PNs. The time course of the subthreshold responses differed strongly between cells. ~60% of the INs showed an early PSP peak, on average at 17.4 +/- 2.4 ms, and ~40% showed a later PSP peak at 77 +/- 33ms. Subthreshold responses in INs often also showed hyperpolarizing components that became visible at depolarized potentials around -55 to -50mV. Suprathreshold responses ranged from 0 to 1.21 APs/stim/100ms for INs and from 0 to 0.45 APs/stim/100ms for PNs. All INs together responded on average with 0.2+/-0.06 APs/stim/100ms and PNs with 0.09 +/-0.14 APs/stim/100ms. Although INs on average responded with more than twice as many APs than PNs, this was mainly due to a subpopulation of ~15% of the INs responding with very high reliability (0.62 +/- 0.13 APs/stim/100ms). This shows that a small group of INs is reliably activated during sensory input, suggesting that prevailing inhibition rather than a lack of excitation prevents PNs in L2/3 from responding stronger.}, web_url = {http://www.sfn.org/am2012/}, event_name = {39th Annual Meeting of the Society for Neuroscience (Neuroscience 2009)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Schmitt AC{aschmitt}{Research Group Neural Population Imaging}; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Sakmann B; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ HaydonWallaceK2009, title = {Two-photon imaging of activity evoked in populations of neurons by simple visual stimuli in the primary visual cortex of awake rats}, year = {2009}, month = {10}, volume = {39}, number = {353.7}, abstract = {Two-photon imaging of the activity of populations of neurons allows detailed investigation of potential population coding strategies used by networks of cortical neurons to represent sensory stimuli and how individual neurons may contribute to this representation. Recent studies from several groups have used this approach to examine evoked responses in populations of neurons in primary sensory areas in anaesthetized animals. We have extended these investigations here to examine the representation of simple visual stimuli in populations of superficial neurons in the primary visual cortex of awake rats. Rats were trained to tolerate sessions of headfixation of sufficient length to allow loading of neurons with the Ca2+-sensitive indicator OGB-1 and subsequent recording of responses to basic visual stimuli (drifting gratings and moving lines). Bolus loading of the OGB-1 was targeted to the cortical area representing the visual space around the vertical meridian and directly in front of the animals nose using optical intrinsic signal imaging and was confirmed subsequently via receptive field mapping of the loaded area using local field potential recording through the loading pipette. Movements of the eyes were monitored using an infra-red camera mounted close to each eye. Drifting grating stimuli of different angles evoked strong activity in discrete subsets of neurons which were scattered in the field of view (ie not organized into specific areas for different angles), as described previously for anaesthetized rodents. Movements of the eyes were not systematically observed during the experiments, though rapid shifts of the position of the pupil, usually in the rostral-caudal plane, were occasionally observed, particularly if the animal was startled. We also found no evidence for systematic movements of the pupil to follow a moving object, such as a line or bar. The experimental setup also allowed for the animal to be anaesthetized during the recording, thus allowing direct comparison of the stimulus responses of the same neurons with the animal under anaesthesia. Additionally, the setup allowed simultaneous whole-cell or cell-attached electrophysiological recordings that could be used to assess the sensitivity of the Ca2+-imaging data for detecting individual action potentials. Using this approach, we aim to provide further insights into coding strategies employed by the visual cortex in awake rats and to what extent these strategies can be inferred from recordings made in anaesthetized animals.}, web_url = {http://www.sfn.org/am2012/}, event_name = {39th Annual Meeting of the Society for Neuroscience (Neuroscience 2009)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Haydon Wallace DJ{dhw}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ SawinskiWGGDK2009, title = {Two-photon imaging of neuronal populations in the visual cortex of freely-moving animals}, year = {2009}, month = {10}, volume = {39}, number = {353.11}, abstract = {While the neuronal basis of certain behaviors and sensory modalities can be studied under anesthesia or head-fixation, the full gamut of neural activity and its functions is accessible only in awake and unrestrained animals. We therefore developed a miniaturized, head mounted 2-photon microscope or “fiberscope” capable of resolving functional action-potential derived fluorescent signals from individual cortical cells. Using the fiberscope, we imaged spontaneous and stimulus-evoked activity from populations of layer 2/3 neurons and astrocytes in the visual cortex in both anesthetized and freely moving rats. The fiberscope weighs 5.5 g, and employs a custom-designed water immersion lens and a non-resonant fiber scanner leveraged by a piezo-element. Excitation light is delivered to the mobile animal through a single-mode optical fiber. Emitted light is collected through a plastic optical fiber before being split into a green channel, for the calcium-indicator Oregon Green BAPTA-1 (OGB1), and a red channel for the specific astrocyte marker sulforhodamin-101. Images acquired through the fiberscope were stable through a range of behaviors, even when the animal is moving vigorously (> 0.6 m/s). Using optical intrinsic imaging to locate the visual cortex binocular region, OGB1 was bulk loaded into cells within this region and remained viable over the course of the four hour experiments. Movement-based artifacts were small and could be successfully corrected offline using custom built software. Fiberscope imaging of neurons under anesthesia revealed robust stimulus responses and orientation selectivity. For imaging in freely-moving animals, the rat was allowed to run in a rectangular arena with one wall made of transparent Perspex behind which static visual stimuli were presented on a CRT monitor. Imaging sessions were run in darkness and recorded using infra-red videography. Transients could be observed in a subgroup of cells in response to activation of the visual stimulus. Further, movements of the animal which resulted in the stimulus sweeping through the animals visual field also evoked transients in a subgroup of the imaged cells. Thus, the miniaturized two-photon fiberscope can record spontaneous and stimulus-evoked Ca2+ transients in freely moving animals. We expect that the fiberscope will facilitate the study of neuronal population activity of during complex behavioral tasks.}, web_url = {http://www.sfn.org/am2012/}, event_name = {39th Annual Meeting of the Society for Neuroscience (Neuroscience 2009)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Sawinski J{jsaw}{Research Group Neural Population Imaging}; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Grossmann S; Denk W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ MeyerzumAltenBorglohWAYBKMGNMPTSKDH2008, title = {Detection of single action potentials in vitro and in vivo with genetically-encoded Ca2+ sensors}, year = {2008}, month = {11}, volume = {38}, number = {496.7}, abstract = {Measurement of population activity with single-neuron resolution is pivotal for understanding how information is represented and processed in the brain and how the brain's responses are altered by experience. Because neuronal activity in the neocortex is sparse and different neuron types perform different tasks, such measurements need to resolve single action potentials in single neurons, and need to be targeted to neuronal sub-classes. This is greatly facilitated by the use of genetically-encoded fluorescent calcium indicator proteins (FCIPs) of neuronal activity. We have employed recombinant adeno-associated viruses to deliver different FCIPs to neurons at a sufficiently high levels to detect the Ca2+ transients that accompany single action potentials. Based on these transients we were able to detect action potentials with high reliability not only in cultured brain slices but also in cortical layer 2/3 pyramidal cells in living animals. Cell-type targeting and long-term recording thus make FCIPs highly suitable to follow the activity of identified cells over the periods of weeks to months. This allows the study of the development and plasticity of neural maps. Preliminary results suggest that with FCIPs functional imaging of the same cells is possible over periods of at least 2 weeks.}, web_url = {http://www.sfn.org/am2012/}, event_name = {38th Annual Meeting of the Society for Neuroscience (Neuroscience 2008)}, event_place = {Washington, DC, USA}, state = {published}, author = {Meyer zum Alten Borgloh S; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Astori S; Yang Y; Bausen M; K\"ugler S; Mank M; Griesbeck O; Nakai J; Miyawaki A; Palmer AE; Tsien RY; Sprengler R; Kerr JND{jkerr}{Research Group Neural Population Imaging}; Denk W; Hasan MT} } @Poster{ KostenGBK2008, title = {Going to temporal superresolution for AP detection in two{photon calcium imaging in vivo by using an explicit datamodel}, year = {2008}, month = {10}, volume = {9}, number = {12}, abstract = {Two{photon calcium imaging in vivo allows for the simultaneous imaging of activity in populations of cortical neurons. This approach has been shown to achieve both single action{potential (AP) and single{cell resolution, an important requirement when measuring neural activity. However, there still remains room for improvement in both data acquisition and data analysis. Imaging calcium transients across time allows the inference of electrical spiking activity, but since the calcium signals are an order of magnitude slower than the spiking activity which produces them, temporal accuracy can be lost. Here we describe a possible approach to increase the temporal resolution of such data. We present an approach that explicitly models signal and noise in the data, and complements the output of a previous spike detection algorithm. Instead of averaging the signal over 96 ms (a full frame), we employ higher resolution that averages over 1.5 ms periods, corresponding to the individual laser scan lines that compose a single image frame. The difference between theoretical and observed fluorescence measurements is modeled as a multivariate Gaussian distribution with zero mean, yielding a likelihood value for each possible spike time over a two frame window. Taking into account the prior distribution of timing errors in the output of our AP detection algorithm, we estimate the detected spike's most likely position. This approach improves temporal resolution significantly compared to previous methods. We discuss the future development of this approach, its limitations, and the crucial role of an accurate estimation of baseline uorescence.}, event_name = {9th Conference of the Junior Neuroscientists of Tübingen (NeNa 2008)}, event_place = {Ellwangen, Germany}, state = {published}, author = {Kosten J{jkosten}{Department High-Field Magnetic Resonance}; Greenberg D{david}{Research Group Neural Population Imaging}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Poster{ GreenbergK2007, title = {Correction of rapid movement induced distortions in two-photon population imaging of awake animals}, year = {2007}, month = {11}, volume = {37}, number = {533.8}, abstract = {In vivo two-photon microscopy (TPM) using bulk-loaded calcium dyes allows recording of spiking activity in dozens of neurons simultaneously. This relatively noninvasive technique has been used previously in anaesthetized animals, and an extension to awake animals, both head-fixed and freely moving, is desirable. However, brain tissue in awake animals frequently moves relative to the objective lens with such speed as to cause displacements during individual frames. These rapid motions induce unique, non-rigid, and non-uniform distortions that warp the image frame and prevent accurate extraction of fluorescence kinetics. Such nonlinear distortions cannot be corrected by rigid (affine) transformations such as translation, uniform stretching, or rotation. To overcome this obstacle, we present here an algorithm for detection and correction of both fast and slow displacements and its application to neuronal population activity collected from awake animals. Our motion correction algorithm operates “blind,” relying only on sequences of imaging frames without measurement of motion, heartbeat, respiration, or muscular tension. We parameterize displacement velocity discretely in time, and use the Lucas-Kanade algorithm to solve for time-displacement functions. Additionally, we describe several further optimizations to maximize speed and accuracy, and derive a formula for true distances between image features applicable even when every frame is heavily motion-distorted. In imaging recorded at 96 ms per frame, the algorithm solves for displacement with < 5 ms temporal resolution. Once motion correction is complete, ROI tracking, deblurring of time averaged images larger than the instantaneous field of view, extraction of calcium transients, and determination of AP times are achieved with negligible computational cost. We applied our motion correction algorithm to in vivo TPM population imaging of visual cortex in awake head-fixed and anesthetized rats. The algorithm successfully detected and corrected movements on multiple timescales, including slow drift over several minutes, regular 2-6 Hz oscillations of 1-4 µm corresponding to respiration and heartbeat rhythms, and fast impulses of over 10 µm in under 50 ms occurring mainly during pronounced motor activity. Fast impulses were ubiquitous in all recordings of head-fixed awake animals. Oscillations in anaesthetized animals also occasionally caused significant displacement within 96 ms, especially when larger craniotomies were employed. Without motion correction, detection of AP times would not have been possible in these imaging sessions.}, web_url = {http://www.sfn.org/am2012/}, event_name = {37th Annual Meeting of the Society for Neuroscience (Neuroscience 2007)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Greenberg DS{david}{Research Group Neural Population Imaging}; Kerr JN{jkerr}{Research Group Neural Population Imaging}} } @Poster{ PawlakK2007, title = {Dopamine receptor activation determines spike timing dependent plasticity (STDP) in the neostriatum}, year = {2007}, month = {11}, volume = {37}, number = {146.13}, abstract = {Single spikes are known to back-propagate into higher-order dendrites of striatal spiny projection neurons both during cortically driven Up-states and during Down-states. The timing of these back-propagating spikes relative to these arriving corticostriatal excitatory inputs determines dendritic calcium concentrations. Both, back-propagating spikes and changes in calcium concentration are required for synaptic plasticity to occur in the cortex. The question arises to whether single spikes can induce long-term synaptic plasticity at the corticostriatal synapse, and whether changes in spike-timing relative to cortical inputs determine the outcome of this plasticity. Here we show that timing of postsynaptic single spikes relative to the arriving corticostriatal excitatory postsynaptic potential (EPSP) determines both direction and strength of synaptic plasticity in spiny projection neurons (n = 110 neurons). Single spikes occurring 30 ms before the cortically evoked EPSP induced strong long-term depression (LTD) (-28 ± 8%, 20-30 min post STDP protocol, n = 12) whereas spikes arriving 10 ms after the EPSP evoked long-term potentiation (LTP) (30 ± 11%, n = 11). These changes in synaptic efficacy decreased as the time between spikes and EPSPs was increased respectively. In addition, we show that STDP is under the strict control of dopamine receptors. Dopamine D1 receptor activation was necessary for both the increase and decrease of synaptic strength, as blocking dopamine D1 receptors prevented LTD induction (3 ± 9%, n = 7), as well as LTP induction (2 ± 4%, n = 9). In contrast, application of dopamine D2 antagonist delayed, but did not prevent LTD (-16 ± 10%, n = 6), and additionally did not change the induction of LTP (32 ± 12%, n = 8). We conclude: 1) in combination with cortical inputs, single spikes in striatal spiny projection neurons can induce both LTP and LTD of the corticostriatal pathway. 2) both the strength and direction of these changes depend deterministically on the spike-timing relative to the arriving cortical inputs. 3) striatal STDP depends on dopamine D1 receptor activation.}, web_url = {http://www.sfn.org/am2012/}, event_name = {37th Annual Meeting of the Society for Neuroscience (Neuroscience 2007)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Pawlak V{vpawlak}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ KerrGH2007, title = {Population imaging of ongoing neuronal activity in visual cortex of the awake rat}, year = {2007}, month = {11}, volume = {37}, number = {920.5}, abstract = {Although prevailing thought holds that neuronal spiking activity decreases from the awake state to the anesthesia induced state, changes in population dynamics during this transition are not understood. Extracellular unit recordings have enabled simultaneous measurements from multiple neurons but suffer from poorly defined cell identities, lack of spatial resolution, a bias toward higher firing rates, and the inability to resolving non-active neurons. Thus, arousal-related changes in synchrony and firing rate in local populations of cortical neurons remain unclear, as does the spatial organization of these activity changes. We used two-photon calcium-imaging to record neuronal spiking activity in the same layer 2/3 populations in visual cortex of awake and anesthetized rats. In addition, using cell-attached recordings from the anesthesia state, we were able to estimate with about 90% accuracy the number of action potentials in each calcium transient, allowing comparison of spike rates between awake and anesthetized states. Average neuronal firing rates remain low in awake (0.30 +/- 0.01 Hz, n = 297 neurons) and anesthetized states (0.21 +/- 0.01 Hz, n = 136 neurons). Although on average firing rates were higher in the awake state, only 60% of neurons decreased their firing upon anesthesia, whereas 40% increased their firing. Firing rate changes brought on by anesthesia in individual neurons depended directly on their prior awake firing rates. Neurons that fired at higher rates in the anesthetized state exhibited decreased firing in the awake state. AP firing was significantly less synchronous in the awake state, both in neuronal pairs and in larger populations. There was no relationship between the strength of pairwise correlations in the awake and anesthetized states, suggesting that changes in arousal state can reset functional connectivity. In both awake and anesthetized states, simultaneous firing of many neurons occurred significantly more often than would be expected from populations of independent neurons. Together this shows that although synchrony and firing rates are both modulated by arousal state at the population level, individual neurons within the population respond heterogeneously and independently.}, web_url = {http://www.sfn.org/am2012/}, event_name = {37th Annual Meeting of the Society for Neuroscience (Neuroscience 2007)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Kerr JN{jkerr}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Houweling AR} } @Poster{ GreenbergHK2007, title = {Stimulus reconstruction from in vivo spiking activity of neuronal populations in somatosensory cortex}, year = {2007}, month = {2}, pages = {285}, abstract = {Sensory stimulation leads to distributed activity across a wide population of neurons in the mammalian somatosensory cortex. It is presumed that information about the sensory stimulus is likewise distributed across a population of neurons, but it remains unknown how information content grows with the number of neurons in the observed population. We aimed to predict the onset times and angles of individual whisker deflections from the activity of simultaneously recorded layer 2/3 neuronal populations, in vivo. Layer 2/3 neurons located above the layer 4 barrel were bulk loaded with the calcium sensitive indicator Oregon-green BAPTA-1 AM and imaged using 2-photon microscopy (TPM). TPM allowed us to monitor both spiking and non-spiking neurons within these populations with single action-potential and single neuron resolution. In addition, this spiking activity was related back to neuron position within the somatotopic map with high (<5 μm) spatial resolution. We then evaluated several techniques for stimulus information extraction from neuronal activity patterns, ultimately deciding on a correlation based algorithm for its simplicity and effectiveness. We used this method to predict the time and angle of whisker deflection from neuronal population activity. We found that the activity of one neuron alone allowed for prediction accuracy only slightly above chance levels. However, as the number of simultaneously recorded neurons that were included in the analysis was increased, prediction errors of both type I (false positives) and type II (undetected stimuli) decreased. We defined a measure of the total extractable information based on the mutual information of Shannon, and found that this quantity increases linearly with the number of available neurons. Using the spatial discrimination capacity of TPM, we observed a highly significant increase in accuracy for the prediction of stimulus onset times among neuronal populations inside the barrel column, as opposed to those in the septal area between barrel columns. However, this anatomical difference was not evident for the prediction of stimulus angle. Both individual neurons and local neuron populations varied widely in the relative amounts of information they contributed about the stimulus. By extrapolating these results to a larger population of neurons, we were able to estimate that near perfect reconstruction of stimulus onset time could be accomplished with between 175 and 201 Layer 2/3 neurons, while reconstruction of stimulus angle could be accomplished with between 244 and 291 neurons. We conclude that sensory inputs to the barrel cortex can be accurately reconstructed from a relatively small population of layer 2/3 neurons, and that stimulus features that are not available in the activity of any individual neuron can be faithfully represented by neuronal populations.}, web_url = {http://www.cosyne.org/c/index.php?title=Cosyne_07}, event_name = {Computational and Systems Neuroscience Meeting (COSYNE 2007)}, event_place = {Salt Lake City, UT, USA}, state = {published}, author = {Greenberg D{david}{Research Group Neural Population Imaging}; Helmchen F; Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2016_2, title = {Using 2-photon microscopy with simultaneous head eye tracking in freely moving animals to quantify the brain in action}, year = {2016}, month = {7}, day = {6}, pages = {3320}, web_url = {http://emdstudio.co.il/ebook/fens2016/files/downloads/FENS%202016%20Programme%20Book.pdf}, event_name = {10th FENS Forum of Neuroscience}, event_place = {Copenhagen, Denmark}, state = {published}, author = {Kerr J{jkerr}} } @Conference{ Kerr2015_2, title = {Turning calcium transients into spikes and watching the animal in action}, year = {2015}, month = {10}, day = {5}, pages = {39}, abstract = {Multiphoton-imaging allows unambiguous access to neuronal populations and neuronal substructures located well below the cortical surface. In combination with genetically encoded activity indicators this approach can be used to infer spiking activity from neuronal populations in the awake animal, with single cell and single action-potential accuracy. I will present recent imaging and analysis tools that are necessary to accurately record activity from genetically encoded calcium indicators in neuronal populations using the multi-photon excitation principle. I will also outline strategies that have allowed access to neuronal activity in the freely moving animal using multiphoton excitation and recent advances to simultaneously track the precise head and eye positions of these freely behaving animals.}, web_url = {http://frontiersneurophotonics.org/documents/fins2015_program_web.pdf}, event_name = {4th International Frontiers in Neurophotonics Symposium (FINS 2015)}, event_place = {Québec, Canada}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2015_3, title = {Imaging populations in the awake animal}, year = {2015}, month = {9}, pages = {35}, abstract = {Multiphoton-imaging allows unambiguous access to neuronal populations and neuronal substructures located well below the cortical surface. In combination with genetically encoded activity indicators this approach can be used to infer spiking activity from neuronal populations in the awake animal, with single cell and single action-potential accuracy. For this lecture I will present imaging tools that are necessary to accurately record activity from neuronal populations in the awake behaving animal using the multi-photon excitation principle. I will also outline strategies that have allowed access to neuronal activity in the freely moving animal and in deep cortical layers. In addition, I will outline recent strategies to simultaneously track the precise head and eye positions of freely behaving animals.}, web_url = {http://www.ptbun.org.pl/file/Abstrakty2015.pdf}, event_name = {12th International Congress of the Polish Neuroscience Society (PNS 2015)}, event_place = {Gdansk, Poland}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2015, title = {Imaging Neuronal and Behavioral Activity in the Freely Moving Animal: What Are They Looking At?}, year = {2015}, month = {3}, day = {19}, web_url = {https://www.grc.org/programs.aspx?id=13542}, event_name = {Gordon Research Conference: Dendrites: Molecules, Structure & Function - How Development and Experience Shape the Computational Properties of Dendrites}, event_place = {Ventura, CA, USA}, state = {published}, author = {Kerr J{jkerr}} } @Conference{ Kerr2013_9, title = {Imaging Activity in the Freely Moving Animal: from the Eye to the Cortex}, year = {2013}, month = {12}, day = {2}, web_url = {https://www.leopoldina.org/fileadmin/redaktion/Veranstaltungen/Symposien/iasfinalprogram130613.pdf}, event_name = {The 3rd Joint Inter-Academy Symposium of the Israel Academy of Sciences and Humanities and the German National Academy of Sciences, Leopoldina}, event_place = {Jerusalem, Israel}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013_3, title = {What are they looking at? Imaging activity in the freely moving rodent from the eye to the cortex}, year = {2013}, month = {11}, day = {13}, volume = {43}, number = {790.06}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013_10, title = {Imaging Neuronal and Behavioural Activity in the Freely Moving Animal: What are they looking at?}, year = {2013}, month = {10}, day = {14}, web_url = {http://talks.cam.ac.uk/show/archive/6140}, event_name = {University of Cambridge: Adrian Seminars in Neuroscience}, event_place = {Cambridge, UK}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013_4, title = {Rats! What are they looking at?}, year = {2013}, month = {8}, day = {30}, web_url = {http://www.caesar.de/978.html}, event_name = {3rd International caesar Conference "Chasing the Neuronal Ensemble II": Center of Advanced European Studies and Research}, event_place = {Bonn, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013, title = {Rats! What are they looking at?}, year = {2013}, month = {7}, day = {23}, event_name = {Max Planck Institute for Biological Cybernetics}, event_place = {Tübingen, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013_5, title = {Imaging neuronal and behavioral activity in the freely moving animal: What are they looking at?}, year = {2013}, month = {6}, day = {17}, web_url = {http://www.rmn2.de/jun-17/}, event_name = {Max Planck Institute for Brain Research}, event_place = {Frankfurt a.M., Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013_8, title = {Imaging neuronal and behavioral activity in the freely moving animal: What are they looking at?}, year = {2013}, month = {6}, day = {11}, web_url = {https://digest.dgsom.ucla.edu/digest/posting-view?digest_id=3022&posting_id=3670033}, event_name = {Leica Scientific Forum US - Los Angeles: Advances in Life Science}, event_place = {Los Angeles, CA, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013_7, title = {Imaging neuronal and behavioral activity in the freely moving animal: What are they looking at?}, year = {2013}, month = {6}, day = {10}, web_url = {https://www.facebook.com/UCSDneurosciences/posts/615399391812454}, event_name = {UC San Diego School of Medicine: Department of Neurosciences}, event_place = {San Diego, CA, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013_6, title = {Imaging neuronal and behavioral activity in the freely moving animal: What are they looking at?}, year = {2013}, month = {5}, web_url = {http://2013.occam-os.de/videos.html}, event_name = {Osnabrück Computational Cognition Alliance Meeting on "The Brain as a Self-Organized Dynamical System" (OCCAM 2013)}, event_place = {Osnabrück, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2013_2, title = {What are they looking at? Imaging activity in the freely moving rodent from the eye to the cortex}, year = {2013}, month = {3}, day = {15}, pages = {10}, abstract = {Rats are binocular animals and although their eyes are located laterally on the head they have a very large region of binocular overlap that extends from below their snouts to behind their head. How this enormous binocular field behaves as the animal navigates through an environment and what advantage this provides is completely unknown because to date there have been no recordings of the movements of both eyes in a freely moving rodent. Eye movements in head-restrained rats are conjugate similar to those of primates, but studies of the vestibular-ocular reflex in rats suggest that this only describes a fraction of their eye movements. Our lab studies how rodents use their vision to make decisions and the cortical circuits that are activated. Studying the cortex in the freely moving animal gives not only gives access to the suite of systems that allows the animal to make sense of the surrounding environment but it also enables the measurement of the behavioral strategies the animal uses when making decisions. In order to measure both activity from cortical populations and head and eye positions in the freely moving animal we further developed our miniature 2-photon microscope to include two lightweight cameras for ocular videography and a head tracking system. Using this approach we show that movements of the two eyes in freely moving rats differ fundamentally from the precisely controlled eye movements used by other mammals to maintain continuous ocular alignment.}, web_url = {https://www.nwg-goettingen.de/2013/default.asp?id=4}, event_name = {10th Göttingen Meeting of the German Neuroscience Society, 34th Göttingen Neurobiology Conference}, event_place = {Göttingen, Germany}, state = {published}, author = {Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2016, title = {Imaging activity in the freely moving animal: from the eye to the cortex}, year = {2012}, month = {12}, day = {4}, abstract = {Motivation underlies the performance of self-determined behavior and is fundamental to decision making, especially with regard to seeking food, mates, and avoiding peril. As many decision making based behaviors in rodents involve a combination of head movements, vestibular driven eye movements, vestibular driven cortical activity and multimodal active sensing of the environment to guide their behavior, studying the freely moving animal is paramount. What is also necessary is the precise tracking of the animal’s movement and interaction with the environment. Here I will outline work from our group that focuses on how rodents use their vision while freely moving and how this this translates to cortical activity. I will introduce methods that allow accurate recording of neuronal activity from populations of cortical neurons, using multiphoton imaging techniques, while simultaneously tracking behavior, using eye and head tracking techniques, during decision making in the freely moving rodent.}, web_url = {https://www.bcf.uni-freiburg.de/events/bernstein-seminar/20121204-kerr}, event_name = {The Bernstein Center Freiburg: Bernstein Seminar}, event_place = {Freiburg, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2012_5, title = {What are you looking at? Imaging eye and cortical activity in the freely moving animal}, year = {2012}, month = {9}, day = {13}, web_url = {http://paris-neuroscience.fr/sites/paris-neuroscience.fr/files/imce/Evenements/programme_enp_days_2012.pdf}, event_name = {École des Neurosciences: 2012 ENP Days}, event_place = {Les Vaux-de-Cernay, France}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2012_3, title = {Two-photon imaging of neuronal populations in vivo: turning calcium bumps into spikes}, year = {2012}, month = {9}, day = {12}, web_url = {http://www.neuroinformatics2012.org/}, event_name = {5th INCF Congress of Neuroinformatics}, event_place = {München, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2012_4, title = {Imaging Neuronal Activity In The Freely Moving Animal: From The Eye To The Cortex}, year = {2012}, month = {7}, day = {16}, abstract = {Motivation underlies the performance of self-determined behavior and is fundamental to decision making, especially with regard to seeking food, mates, and avoiding peril. As many decision making based behaviors in rodents involve a combination of head movements, vestibular driven eye movements, vestibular driven cortical activity and multimodal active sensing of the environment to guide their behavior, studying the freely moving animal is paramount. In this presentation I will outline work from our group that focuses on recording neuronal activity from populations of cortical neurons, using multiphoton imaging techniques, while simultaneously tracking behavior, using eye and head tracking techniques, during decision making inthe freely moving rodent.}, web_url = {http://fens2012.meetingxpert.net/FENS_331/poster_32614/program.aspx/anchor32614}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2012_2, title = {Imaging active neuronal circuits in the freely moving animal: seeing what they see from the eye to the cortex}, year = {2012}, month = {5}, day = {15}, web_url = {http://www.cin.uni-tuebingen.de/news-events/browse-all-events/detail/view/338/page/1/conference-fin-building-inauguration-symposium-new-perspectives-in-integrative-neuroscience.html}, event_name = {FIN Building Inauguration Symposium: New Perspectives in Integrative Neuroscience}, event_place = {Tübingen, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2012, title = {Areal Distribution Of The Von Economo In The Anterior Insular And Anterior Cingulate Cortices In The Macaque Monkey}, year = {2012}, month = {3}, day = {16}, event_name = {University of Edinburgh: Centre for Integrative Physiology}, event_place = {Edinburgh, UK}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2011_3, title = {2-photon imaging of neuronal activity in freely moving animals: from the eye to the visual cortex during self-determined behavior}, year = {2011}, month = {11}, day = {22}, web_url = {http://www.science.fau.edu/neuroscience/iban/seminars.htmlBAK}, event_name = {FAU/MPFI Neuroscience Seminar Series Fall 2011: Neural Circuits at Multiple Scales}, event_place = {Jupiter, FL, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2011_2, title = {Imaging activity from neuronal populations in the awake and freely moving rat}, year = {2011}, month = {9}, day = {5}, web_url = {http://events.embo.org/11-two-photon/programme.html}, event_name = {EMBO Practical Course: Two-Photon Imaging of Brain Circuits}, event_place = {München, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2011_4, title = {2-photon imaging of neuronal activity in freely moving animals: from the eye to the visual cortex during self determined behavior}, year = {2011}, month = {7}, day = {19}, web_url = {https://www.fmi.ch/news/seminars/?d=7/1/2011&evtCat=All}, event_name = {Friedrich Miescher Institute for Biomedical Research}, event_place = {Basel, Switzerland}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2011, title = {Imaging neuronal population activity in the cortex of freely moving animals: The what where and how}, year = {2011}, month = {4}, day = {4}, web_url = {https://www.janelia.org/sites/default/files/You%20%2B%20Janelia/Conferences/agenda_conf-056.pdf}, event_name = {HHMI Janelia Research Campus: Multiphoton Imaging: The Next 6x1023 Femtoseconds}, event_place = {Ashburn, VA, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2010, title = {Release the Hounds: Imaging Activity in Neuronal Populations in the Freely Moving Animal}, year = {2010}, month = {10}, day = {1}, web_url = {http://online.kitp.ucsb.edu/online/neuro10/}, event_name = {Kavli Institute for Theoretical Physics Program: Emerging Techniques in Neuroscience}, event_place = {Santa Barbara, CA, USA}, state = {published}, author = {Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2010_2, title = {Releasing the Hounds: Imaging Activity in Neuronal Populations in the Freely Moving Animal}, year = {2010}, month = {6}, day = {8}, web_url = {http://calendar.med.nyu.edu/index.cfm?fuseaction=SOMCalendar.DisplaySeminarPoster&FuseCalendar_ID=67542&CFID=259147&CFTOKEN=29366516}, event_name = {New York University School of Medicine, NYU Medical Center}, event_place = {New York, NY, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2010_3, title = {Releasing the hounds: population imaging in the freely moving animal}, year = {2010}, month = {4}, day = {13}, web_url = {http://www.cin.uni-tuebingen.de/news-events/browse-all-events/detail/view/338/page/3/conference-cin-retreat-cellular-neurophysiology.html}, event_name = {CIN-Retreat Cellular Neurophysiology}, event_place = {Reutlingen, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2009, title = {Would the real inhibitor please stand up: imaging neural populations in vivo}, year = {2009}, month = {3}, day = {2}, abstract = {The role of inhibitory neurons embedded in neuronal circuits during spontaneous and evoked activity is far from being understood as their basic properties, such as spontaneous firing and evoked response rates, are not well characterized. I will present findings from our lab that addresses the role of identified inhibitory and excitatory neurons during sensory stimulation and discuss the implications of their properties on sensory processing within a cortical column.}, web_url = {http://www.cosyne.org/c/index.php?title=The_role%28s%29_of_inhibition_and_excitatory/inhibitory_balance_in_sensory_processing}, event_name = {Cosyne 2009 Workshop: The role(s) of inhibition and excitatory/inhibitory balance in sensory processing}, event_place = {Snow Bird, UT, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2008, title = {Imaging activity in cortical neuronal populations in vivo: from the anesthetized to the awake}, year = {2008}, month = {6}, day = {24}, web_url = {http://www.chaos.gwdg.de/events/nldseminar.2008-03-17.2958988223}, event_name = {Nonlinear Dynamics Groups at the Max Planck Institute for Dynamics and Self-Organization: BCCN AG-Seminar}, event_place = {Göttingen, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2007, title = {Spatial Organization of Neuronal Population Responses in vivo: can you repeat that?}, year = {2007}, month = {10}, day = {31}, abstract = {Although individual pyramidal neurons of neocortex show sparse and variable responses to sensory stimuli in vivo, it has remained unclear how this variability extends to population responses on a trial-to-trial basis. Two-photon imaging allows the study of both form and function in populations of neurons, in vivo, while taking into account all the neurons within a local area, whether actively spiking or not. Here I will present data from ongoing studies in which we characterized single-neuron and neuronal population activity of layer 2/3 neurons located in identified columns in rat barrel cortex. First, optical detection of single action potentials from evoked calcium transients revealed low spontaneous firing rates, and variable response probabilities. Second, neuronal pairs showed correlations in both spontaneous and sensory-evoked activity that depended on the location of the neurons. Thus, even though neurons were not activated independently, precisely repeating spatial activation patterns were not observed. Instead, population responses showed large trial-to-trial variability. Nevertheless, the accuracy of decoding stimulus onset-times from local population activity increased with population size and depended on anatomical location. In conclusion, despite their sparseness and variability L2/3 population responses show a clear spatial organization on the columnar scale.}, web_url = {http://redwood.berkeley.edu/seminar-info.php?id=69}, event_name = {University of California: Redwood Center for Theoretical Neuroscience}, event_place = {Berkeley, CA, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2006, title = {Combining two-photon imaging with electrophysiology in vivo: from the synapse to the network}, year = {2006}, month = {7}, pages = {208P}, abstract = {Understanding how information is represented and processed in the mammalian neocortex requires measurement of spatiotemporal activity patterns in identified networks of neurons in vivo. What will be required is the ability to be simultaneously record both input and output of cortical microcircuits with single-cell and single-spike resolution. Recently, two-photon laser scanning microscopy (2PLSM) has provided a viewing window into the in vivo brain. The advantages of multi-photon laser excitation combined with in vivo bulk labeling techniques have been exploited to image both cellular and subcellular structures within the mammalian brain on time scales ranging from milliseconds to weeks. Bulk loading of brain tissue with Acetoxymethyl (AM) ester derivatives of calcium indicators has become a potentially powerful tool in the quest to understand encoding of information in neuronal populations. Several issues arise with the use of this technique: 1) all tissue and structures are labeled with these dyes requiring specific counterstaining with either genetically encoded labels or additional dyes such as astrocyte specific sulforhodamine 101. 2) because of sparse neuronal action-potential (AP) firing in many cortical areas, it is therefore necessary to ensure the detection of single AP evoked calcium signals. In addition, there is a compromise between the spatial/temporal resolution and signal to noise ratio of signal detection. Combining these imaging techniques with simultaneous targeted electrophysiological recordings allows for the probing of neuronal circuits as well as the calibration of neuronal electrical signals with imaging data. Here I will present work that combines both 2PLSM imaging of on-going neuronal population activity and various electrophysiological techniques to simultaneously record neuronal output activity from local neuronal populations with single cell and single AP resolution. In addition, because the neuropil is also loaded using this loading technique, I will also present data showing that the ongoing neuropil signal represents axonal activity and reflects a volume averaged input signal to the local circuit. I will describe how both targeted cell attached and whole-cell recording techniques were used to establish that AP activity is reliably resolved with single-cell and single-AP resolution in bulk-loaded neurons. This made it possible to optically extract AP patterns, representing ‘‘output’’ activity, in local neuronal circuits. These results revealed that spatial organization of active neurons was not stable but displayed considerable heterogeneity over the time course of minutes. This heterogeneity indicated that spontaneous activity does not emerge exclusively in a particular subset of neurons but rather is generated by a continually changing subpopulation of neurons. Spontaneous calcium signals in the neuropil were tightly correlated to electrocorticogram and intracellular membrane potentials of neurons embedded within the local network. This optical encephalogram (OEG) represents bulk calcium signals in axonal structures, and provides a measure of local input activity. Because input–output relationships are of key importance for the understanding of signal processing in neuronal circuits, this optical approach should enable the study of input–output transformations during sensory input and how they are affected by varying levels of background activity such as they occur during different behavioral states.}, web_url = {http://www.physoc.org/proceedings/abstract/Proc%20Physiol%20Soc%203WA1}, event_name = {Meeting of the Physiological Society 2006: Workshop Methodologies in Systems Neuroscience}, event_place = {London, UK}, state = {published}, author = {Kerr JND{jkerr}} }