@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}{Research Group Neural Population Imaging} and 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 and 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} and 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 and 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 and 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 and 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} and 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 and 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} and 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 and 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 and 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} and 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} and 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 and 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} and Helmchen F} } @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} and 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 and Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ MullerBierlPKUU2012, title = {A realistic vascular model for BOLD signal up to 16.4 T}, year = {2010}, month = {5}, 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 and Uludag K{kuludag}{Department High-Field Magnetic Resonance}} } @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 di erence between theoretical and observed uorescence 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 signi cantly 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.}, web_url = {http://www.neuroschool-tuebingen-nena.de/index.php?id=284}, 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} and Kerr J{jkerr}{Research Group Neural Population Imaging}} } @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 and Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Kerr2012, title = {Imaging activity in neuronal populations in the freely moving animal}, year = {2012}, month = {7}, day = {16}, web_url = {http://www.bacofun.medizin.uni-mainz.de/172.php}, event_name = {BaCoFun at the 8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} }