@Article{ HagbergMPBMVKDKL2013,
title = {Diffusion properties of conventional and calcium sensitive MRI contrast agents in the rat cerebral cortex},
journal = {Contrast Media and Molecular Imaging},
year = {2013},
month = {3},
state = {accepted},
author = {Hagberg G{ghagberg}{Department High-Field Magnetic Resonance}, Mamedov I{ilgar}{Department Physiology of Cognitive Processes}, Power A{apower}{Department Physiology of Cognitive Processes}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Merkle H{hellmut}, Valerij G, Kiseleyd V, Dhingra K{kirti}{Department Physiology of Cognitive Processes}, Kubičeke V and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ DhingraVermaMEBML2012,
title = {Magnetic-Field-Dependent 1H Relaxivity Behavior of Biotin/Avidin-Based Magnetic Resonance Imaging Probes},
journal = {ChemPlusChem},
year = {2012},
month = {9},
volume = {77},
number = {9},
pages = {758–769},
abstract = {One major challenge in noninvasive mapping of various molecular targets is their inherently low in vivo concentration coupled with the insensitivity of imaging modalities, such as the widely used magnetic resonance imaging (MRI). Development of agents with high sensitivity and specificity is of paramount importance for structural and functional noninvasive imaging. The design, synthesis, and physiochemical characterization of two gadolinium-based contrast agents (CAs) for MRI, the sensitivity of which was optimized by exploiting the well-established biotin–avidin amplification strategies, are reported. The relaxivity of these agents showed a large increase if bound to avidin; specifically, the first compound showed an approximately 1000 % increase in transverse proton relaxivity (r2p), whereas the second compound had an approximately 250 % r2p increase. The increase in r2p was magnetic field independent in the range of 1.5–16.4 T whereas the longitudinal proton relaxivity (r1p) showed strong field dependence. The CAs were further characterized by measuring luminescence lifetimes and emission spectral changes upon addition of avidin to their Eu3+ analogues. The difference in relaxation rate behavior of both complexes was explained on the basis of hydration number modulation and the “global/internal motion concept”. The association constant of these CAs with avidin was found to be in the range of approximately 1015 M−1, which shows that the coupling of biotin to Gd-DO3A did not affect its affinity for binding to avidin (DO3A=1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid).},
web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cplu.201200064/pdf},
state = {published},
DOI = {10.1002/cplu.201200064},
author = {Dhingra Verma K{kirti}{Department Physiology of Cognitive Processes}, Mishra A{anuragrk}{Department Physiology of Cognitive Processes}, Engelmann J{joern}{Department High-Field Magnetic Resonance}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Maier ME and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ MamedovEEBL2011,
title = {Dual-functional probes towards in vivo studies of brain connectivity and plasticity},
journal = {Chemical Communications},
year = {2012},
month = {2},
volume = {48},
number = {22},
pages = {2755-2757},
abstract = {A Gd3+ based paramagnetic dextran conjugate has been developed, which enables the tracking of neuroanatomical connectivity in the brain by both MR and optical imaging. Cell studies and subsequent in vivo experiments in rodents demonstrate efficient internalisation and transport properties of the new tracer molecule.},
web_url = {http://pubs.rsc.org/en/Content/ArticleLanding/2012/CC/c1cc15991g},
state = {published},
DOI = {10.1039/C1CC15991G},
author = {Mamedov I{ilgar}{Department Physiology of Cognitive Processes}, Engelmann J{joern}{Department High-Field Magnetic Resonance}, Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ EschenkoENBML2011,
title = {Tracing of noradrenergic projections using manganese-enhanced MRI},
journal = {NeuroImage},
year = {2012},
month = {2},
volume = {59},
number = {4},
pages = {3252–3265},
abstract = {We examined the applicability of manganese-enhanced MRI (MEMRI) to the in vivo tracing of diffuse neuromodulatory projections by means of simultaneous iontophoretic injections of an extremely low, non-toxic concentration of MnCl2 (10 mM) and fluorescent dextran in the locus coeruleus (LC) in the rat. We validated the use of the iontophoretic injection by reproducing previously reported results from pressure injections of MnCl2 in primary somatosensory cortex. Twenty four hours after injection in LC, Mn2 + labeling was detected in major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor and somatosensory cortices, hippocampus and amygdala. Although the injections were in most cases centered in the core of LC, the pattern of Mn2 + labeling greatly varied across rats. In addition, despite a certain degree of overlap of the labeling obtained with both MEMRI and classical tracing, MEMRI tracing consistently failed to reliably label not only several minor but also major targets of LC, notably the thalamus. The lack of Mn2 + labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. Inversely, a number of brain regions, particularly contralateral motor cortex, that were not or only sparsely labeled with fluorescent dextran were strongly labeled by Mn2 +. This discrepancy could be partly due to both the activity-dependent and transsynaptic nature of Mn2 + transport. The overall labeling produced using MEMRI with iontophoretic injections in LC indicates that the Mn2 + imaging of highly diffuse projections is in principle feasible. However, the labeling pattern of each individual case needs to be carefully interpreted particularly before submitting data for group analysis or in the case of longitudinal examination of discrete changes in functional connectivity under various physiological or behavioral conditions.},
web_url = {http://www.sciencedirect.com/science/article/pii/S1053811911013127},
state = {published},
DOI = {10.1016/j.neuroimage.2011.11.031},
author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}, Evrard HC{evrard}{Department Physiology of Cognitive Processes}, Neves RM{ricardo}{Department Physiology of Cognitive Processes}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ MishraSEBLC2011,
title = {Biocytin-derived MRI contrast agent for longitudinal brain connectivity studies},
journal = {ACS Chemical Neuroscience},
year = {2011},
month = {10},
volume = {2},
number = {10},
pages = {578–587},
abstract = {To investigate the connectivity of brain networks noninvasively and dynamically, we have developed a new strategy to functionalize neuronal tracers and designed a biocompatible probe that can be visualized in vivo using magnetic resonance imaging (MRI). Furthermore, the multimodal design used allows combined ex vivo studies with microscopic spatial resolution by conventional histochemical techniques. We present data on the functionalization of biocytin, a well-known neuronal tract tracer, and demonstrate the validity of the approach by showing brain networks of cortical connectivity in live rats under MRI, together with the corresponding microscopic details, such as fibers and neuronal morphology under light microscopy. We further demonstrate that the developed molecule is the first MRI-visible probe to preferentially trace retrograde connections. Our study offers a new platform for the development of multimodal molecular imaging tools of broad interest in neuroscience, that capture in vivo the dynamics of large scale neural networks together with their microscopic characteristics, thereby spanning several organizational levels.},
web_url = {http://pubs.acs.org/doi/pdf/10.1021/cn200022m},
state = {published},
DOI = {10.1021/cn200022m},
author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}, Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}, Engelmann J{joern}{Department High-Field Magnetic Resonance}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Logothetis NK{nikos}{Department Physiology of Cognitive Processes} and Canals S{canals}}
}

@Article{ 6854,
title = {In Vivo Characterization of a Smart MRI Agent That Displays an Inverse Response to Calcium Concentration},
journal = {ACS Chemical Neuroscience},
year = {2010},
month = {12},
volume = {1},
number = {12},
pages = {819-828},
abstract = {Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd3+ complex linked to an aminobis(methylenephosphonate) group for chelating Ca2+ was synthesized and investigated. The longitudinal relaxivity (r1) of this complex decreases during the relaxometric titration with Ca2+ from 5.76 to 3.57 mM−1 s−1 upon saturation. The r1 is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu3+ complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity
of this
agent is
significantly lower compared with that of gadolinium−diethylenetriaminepentaacetic acid (Gd−DTPA).},
web_url = {http://pubs.acs.org/doi/pdf/10.1021/cn100083a},
state = {published},
DOI = {10.1021/cn100083a},
author = {Mamedov I{ilgar}{Department Physiology of Cognitive Processes}, Canals S{canals}, Henig J, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes}, Mayer HA, Logothetis NK{nikos}{Department Physiology of Cognitive Processes} and Angelovski G{goran}{Department Physiology of Cognitive Processes}}
}

@Article{ 6148,
title = {Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies},
journal = {Neuroimage},
year = {2010},
month = {2},
volume = {49},
number = {3},
pages = {2544-2555},
web_url = {http://www.sciencedirect.com/science?_ob=PdfDownloadURL&_uoikey=B6WNP-4XM6K9C-1&_tockey=%23toc%236968%239999%23999999999%2399999%23FLA%23&_orig=search&_acct=C000003178&_version=1&_userid=29041&md5=3bf6091d834384671282cddb6fdb75},
state = {published},
DOI = {10.1016/j.neuroimage.2009.10.079},
author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}, Canals S{canals}, Simanova I, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 5682,
title = {Functional MRI Evidence for LTP-Induced Neural Network Reorganization},
journal = {Current Biology},
year = {2009},
month = {2},
volume = {19},
number = {5},
pages = {398-403},
abstract = {The hippocampal formation is a region of the forebrain that is important for memory and spatial navigation [1] and [2]. On the basis of a vast amount of literature, the hippocampus is linked with long-term potentiation (LTP), the increased synaptic strength following repeated stimulation of the hippocampal neurons [3] and [4]. LTP is considered to be the experimental demonstration of Hebb‘s postulate on synaptic strength and learning [5], and it is the dominant model of an experience-dependent modification of brain circuits. Yet, despite the importance of this phenomenon for brain physiology and behavior, little is known about how experimentally measured regional synaptic modifications alter the activity of global, widespread networks. Here, we use simultaneous fMRI, microstimulation, and electrophysiology [6], [7] and [8] to unveil global changes in brain activity due to local hippocampal plasticity. Our findings offer the first evidence of an LTP-induced network reorganization that includes increased interhemispheric communication and recruitment of limbic and neocortical circuits after changes in synaptic strength within the hippocampus.},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6VRT-4VN6FY0-2-2&_cdi=6243&_user=29041&_orig=search&_coverDate=03%2F10%2F2009&_sk=999809994&view=c&wchp=dGLbVzz-zSkWz&md5=d169ef23b3c11c387440f570325c554a&ie=/sdarticle.pdf},
state = {published},
DOI = {10.1016/j.cub.2009.01.037},
author = {Canals S{canals}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Merkle H{hellmut} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 4909,
title = {Electric stimulation fMRI of the perforant pathway to the rat hippocampus},
journal = {Magnetic Resonance Imaging},
year = {2008},
month = {9},
volume = {26},
number = {7},
pages = {978-986},
abstract = {The hippocampal formation is a brain system that is implicated in learning and memory. The major input to the hippocampus arrives from the entorhinal cortex (EC) to the dentate gyrus (DG) through the perforant path. In the present work, we have investigated the functional properties of this connection by concomitantly applying electrophysiological techniques, deep-brain electric microstimulation and functional magnetic resonance imaging in anesthetized rats. We systematically delivered different current intensities at diverse stimulation frequencies to the perforant path while recording electrophysiological and blood-oxygenation-level-dependent (BOLD) signals. We observed a linear relationship between the current intensity used to stimulate the hippocampal formation and the amplitude and extension of the induced BOLD response. In addition, we found a frequency-dependent spatial pattern of activation. With stimulation protocols and train frequencies used for kindling, the activity strongly spreads ipsilaterall
y through the hippocampus, DG, subiculum and EC.},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4SH1HXR-B-5&_cdi=5112&_user=29041&_orig=search&_coverDate=09%2F30%2F2008&_sk=999739992&view=c&wchp=dGLzVtb-zSkWz&md5=e7e95446b785f4dd0f51d9b02acb372d&ie=/sdarticle.pdf},
state = {published},
DOI = {10.1016/j.mri.2008.02.018},
author = {Canals S{canals}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 5128,
title = {Synthesis and Characterization of a Smart Contrast Agent Sensitive to Calcium},
journal = {Chemical Communications},
year = {2008},
month = {6},
volume = {29},
pages = {3444-3446},
abstract = {A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.},
web_url = {http://www.rsc.org/ej/CC/2008/b801975d.pdf},
state = {published},
DOI = {10.1039/b801975d},
author = {Dhingra K{kirti}{Department Physiology of Cognitive Processes}, Maier ME, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Angelovski G{goran}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 4894,
title = {Magnetic Resonance Imaging of Cortical Connectivity in vivo},
journal = {Neuroimage},
year = {2008},
month = {4},
volume = {40},
number = {2},
pages = {458-472},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WNP-4RC6R7X-4-S&_cdi=6968&_user=29041&_orig=search&_coverDate=04%2F01%2F2008&_sk=999599997&view=c&wchp=dGLbVtz-zSkzS&md5=dabfb44094d1137121dd895184e159cc&ie=/sdarticle.pdf},
state = {published},
DOI = {10.1016/j.neuroimage.2007.12.007},
author = {Canals S{canals}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Keller AL{akeller}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Article{ 2894,
title = {Anatomical and Functional MR Imaging in the Macaque Monkey Using a Vertical Large-bore 7 Tesla Setup},
journal = {Magnetic Resonance Imaging},
year = {2004},
month = {12},
volume = {22},
number = {10},
pages = {1343-1359},
file_url = {/fileadmin/user_upload/files/publications/pdf2894.pdf},
web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4FF9547-2-K&_cdi=5112&_user=29041&_orig=search&_coverDate=12%2F31%2F2004&_sk=999779989&view=c&wchp=dGLzVlz-zSkzk&md5=26f8916c8f8a658f9009cce48bfcedfc&ie=/sdarticle.pdf},
state = {published},
DOI = {10.1016/j.mri.2004.10.004},
author = {Pfeuffer J{josef}{Department Physiology of Cognitive Processes}, Merkle H{hellmut}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Steudel T{steudel}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Inbook{ MishraDMSEBCL2011,
title = {Biocytin-based contrast agents for molecular imaging: an approach to developing new in vivo neuroanatomical tracers for MRI},
year = {2012},
month = {2},
volume = {1},
pages = {181-204},
abstract = {One of the most striking characteristic of the brain is its profuse neuronal connectivity. Not surprisingly, the function of the nervous system critically depends on the spatiotemporal pattern of intercommunication between different regions of the brain. Both macro- and microscopic aspects of the wiring diagrams of brain circuits are relevant and need to be understood in order to cope with the complexity of the brain function. In this way, for
instance, the long-range connections that carry the functional specification of cortical territories need to be studied together with the detailed microcircuits inside a cortical column. Moreover, the temporal dimension of these wiring diagrams must be investigated since neuronal networks are dynamic structures exhibiting context-dependent changes in synaptic weights (Canals et al., 2009) and numbers (Chklovskii et al., 2004). Investigations
over the last decades strongly suggest that stimulus or task related neural activity is distributed over large parts of the brain, covering different cortical and sub-cortical areas. For a detailed understanding of brain function, it is of prime importance to understand the
organization of the neuronal connections. To chart the anatomical connections between the various components of brain networks, the neuronal tract tracing technique has been proved to be very useful. Thus, experimental tools that allow the exploration of brain circuits at diverse organizational levels are mandatory for the understanding of brain intercommunication and information processing.},
web_url = {http://www.intechopen.com/articles/show/title/biocytin-based-contrast-agents-for-molecular-imaging-an-approach-to-developing-new-in-vivo-neuroanat},
editor = {Bright, P.},
publisher = {InTech},
address = {Rijeka, Croatia},
booktitle = {Neuroimaging - Methods},
state = {published},
ISBN = {978-953-51-0097-3},
DOI = {10.5772/23806},
author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}, Mishra R{ritu}{Department High-Field Magnetic Resonance}, Canals S{canals}, Logothetis NK{nikos}{Department Physiology of Cognitive Processes}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Engelmann J{joern}{Department High-Field Magnetic Resonance}, Sch\"uz A{schuez}{Department Physiology of Cognitive Processes} and Dhingra K{kirti}{Department Physiology of Cognitive Processes}}
}

@Poster{ EschenkoBOL2012,
title = {BOLD responses evoked by electrical stimulation of Locus Coeruleus in rats under anesthesia},
year = {2012},
month = {10},
volume = {42},
pages = {674.15},
abstract = {We performed a whole-brain fMRI imaging in the rat under urethane anesthesia and studied BOLD responses induced by electrical stimulation of the brain stem noradrenergic nucleus Locus Coeruleus (LC). The rat was implanted with a MRI-compatible custom-made iridium electrode into LC under electrophysiological guidance. A 7T (300 MHz) magnet with a 30-cm horizontal bore (Bruker BioSpec 70/30, Ettlingen, Germany) equipped with a 20cm inner diameter gradient (Bruker BGA-20S Ettlingen, Germany) was used for MRI scanning. The experimental paradigm consisted of 6s baseline sampling, followed by 4s of unilateral LC stimulation and 10s of post-stimulus sampling. Biphasic square pulses (0.05-0.4mA) were delivered to LC at 20-100Hz either continuously for 4s or grouped in 100-500ms trains. These stimulation parameters were efficient in eliciting LC burst firing bilaterally. We also collected BOLD responses induced by peripheral sensory stimulation in the same animal and using the same experimental design (6/4/10s). For visual stimulation we used a luminance flicker presented to both eyes at 16Hz and delivered via fiber optic cables. A mild electrical stimulation (1-5mA) of a forepaw was used as somatosensory stimulation. The fMRI images were collected with spatial resolution of 0.4x0.4x1.0mm and temporal resolution of 1s. BOLD maps were generated by using GLM with standard (HRF-convolved boxcar functions) or neural regressors. We observed a remarkable dichotomy between BOLD responses of cortical and subcortical structures. Specifically, LC stimulation produced positive BOLD responses in the majority of structures belonging to metencephalon, mesencephalon and diencephalon, while negative BOLD responses in the entire neocortex. The robust neuronal activation in thalamic projections of LC was further confirmed by electrophysiological recordings. The cortical inhibition as a result of LC stimulation and associated NE release in cortical targets of LC has been reported in earlier studies. The peripheral sensory stimulation evoked both sensory-specific and non-specific activation/deactivation pattern. Strikingly, the regions of non-specific BOLD responses were common for both sensory modalities and largely overlapped with brain regions that showed responses to LC stimulation. We hypothesize that sensory stimulation activates modality-specific sensory pathways along with LC-NE system; and the LC co-activation produces the observed non-specific BOLD responses.},
web_url = {http://www.sfn.org/am2012/},
event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)},
event_place = {New Orleans, LA, USA},
state = {published},
author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Oeltermann A{axel} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ NevesEEBL2010,
title = {Mapping noradrenergic projections from locus coeruleus using classical fluorescent tracer and MRI-visible contrast agent},
year = {2010},
month = {7},
volume = {7},
number = {087.13},
abstract = {We examined anterograde labeling of noradrenergic terminals originating from the neurons of brain stem neuromodulatory nucleus Locus Coeruleus (LC), a major course of noradrenaline in the rat forebrain, by means of simultaneous iontophoretic injection of paramagnetic (Mn2+) and classical (fluorescent dextran) tracers in the LC. In order to detect Mn2+ transport, MRI scanning was performed in each rat before and 24h after injection and, subsequently, MR images were compared using voxel-based t-test (voxel size: 0.25x0.25x0.25mm). Fluorescent dextran monosynaptic anterograde transport was analysed 5 days after injection. Iontophoretic injection of Mn2+ did not produce neurotoxic effects as there were no signs of neuronal death or glial inflammatory reaction at the injection site 5 days after injection. Both methods revealed reliable labeling in major subcortical terminal fields of LC neurons (Swanson and Hartman, 1975; Ungerstedt, 1971) including central nucleus of amygdala, internal capsule, anterior part of bed nucleus of the stria terminalis, and mesencephalic region. Consistent with previous studies, labeling was predominantly ipsilateral to the injection site. Classical tracer readily detected terminals like fibers of passage typical for noradrenergic innervation of cortical regions. In contrast, manganese-enhanced MRI (MEMRI) method failed to visualize such dispersed noradrenergic innervation in the cortex. On the other hand, MEMRI might be more sensitive for detecting patterns of functional connectivity. Consistent and strong Mn-labeling in hippocampus was observed, which was not proportional to anatomical connectivity labeled by dextran. Thus, the tract-tracing using MEMRI preferentially maps the target sites of rather strong and highly concentrated projections, but not dispersed terminal fields. Despite the relatively low resolution of MEMRI technique compared to florescent microscopy, this novel tract-tracing method can be successfully applied for visualization of major neural pathways and their reorganization in the same animal in longitudinal studies including those concentrating on development, aging, plasticity, or disease-related neurodegeneration.},
web_url = {http://fens2010.neurosciences.asso.fr/},
event_name = {7th Forum of European Neuroscience (FENS 2010)},
event_place = {Amsterdam, Netherlands},
state = {published},
author = {Neves RM{ricardo}{Department Physiology of Cognitive Processes}, Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}, Evrard H{evrard}{Department Physiology of Cognitive Processes}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ NevesEEBL2009,
title = {Anterograde analysis of noradrenergic projections in the rat forebrain using classical and manganese-enhanced MRI (MEMRI) tract-tracing},
year = {2009},
month = {11},
volume = {10},
number = {10},
pages = {29},
abstract = {We examined anterograde labeling of noradrenergic terminals originating from the neurons of brain stem neuromodulatory nucleus Locus Coeruleus (LC), a major course of noradrenaline in the rat forebrain, by means of simultaneous iontophoretic injection of paramagnetic
(Mn2 +) and classical (fluorescent dextran) tracers in the LC. Both MEMRI and fluorescent microscopy revealed anterograde labeling in major terminal fields of LC neurons
(Swanson and Hartman, 1975; Ungerstedt, 1971) 24 h and 5 d after injection, respectively. Predominantly ipsilateral labeling of thalamic nuclei, primary sensory cortices, medial prefrontal cortex, and olfactory bulbs reflected previously demonstrated monosynaptic projections of
the LC neurons in multiple target brain regions. The labeling patterns of both paramagnetic and classical tracers were strikingly similar. Importantly, iontophoretic injection of Mn2+ did not produce neurotoxic effects as there were no signs of neuronal death or glial inflammatory
reaction at the injection site 5 days after injection. The reported results further validate MEMRI tract-tracing technique allowing visualization a highly distributed and distal efferent projections arising from the brain stem nucleus. Thus, MEMRI may be used for mapping convergent target brain regions of different neuromodulatory systems in the same animal and their functional reorganization in longitudinal studies.},
web_url = {http://www.neuroschool-tuebingen-nena.de/},
event_name = {10th Conference of Junior Neuroscientists of Tübingen (NeNa 2009)},
event_place = {Ellwangen, Germany},
state = {published},
author = {Neves RM{ricardo}{Department Physiology of Cognitive Processes}, Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}, Evrard H{evrard}{Department Physiology of Cognitive Processes}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ DhingraMESCPBML2009,
title = {Development of Bio-responsive Contrast Agents for Magnetic Resonance Imaging: Potential Applications of a Novel Precursor},
year = {2009},
month = {9},
volume = {2009},
number = {0617},
abstract = {Magnetic resonance imaging (MRI) is one of the powerful imaging modality. To circumvent its low sensitivity, there has been a substantial interest on the development of the contrast agents. In the present scenario, there is a need to develop contrast agents which are target specific and can report the changes in the physiological environment around them. On the similar lines we are reporting here a novel precursor (tris-tert-Bu-(Z)-Ser-DO3A (Figure 1)). This precursor contains an amine and a carboxylate groups in an orthogonally protected condition, which allows their selective de-protection and coupling to different moieties. Out of the various possibilities, we explored two strategies of coupling that lead to a potential targeted CA and another CA with potential of tracing neuroanatomy in the brain. The special design of these agents not only provides the stability against their enzymatic degradation which is important for their in vivo applicability but also has the possibility to amplify its signal once recognized by the target site. This could be done by exploiting the biotin/strept(avidin) high affinity and the pretargeting strategy, which is well established in nuclear medicine. The CA when bound to avidin showed an enhancement in the relaxivity (r1 and r2) at 1.5T. A substantial increase of ≥1000% in r2 was observed at all magnetic fields studied (1.5T, 3T, 7T, 9.4T) while r1 showed an increase of 260% at 1.5T and an expected decrease with further increase of field strength. The relaxivity changes at 1.5T suggest the structural requirement of a CA to fit in to avidin and optimize the parameters determining relaxivity of the complex matches well with our synthesized agent. Using the same precursor, we have also synthesized a CA which can potentially be used for tracing the neuronal tracks in the brain. Biocytin was used as the basic tracer. Coupling an MR detectable moiety to a well known neuroanatomical tracer would open up new possibilities to noninvasively study the neuronal networks by MRI.},
web_url = {http://www.wmicmeeting.org/abstracts/data/papers/0617.html},
event_name = {2009 World Molecular Imaging Congress (WMIC)},
event_place = {Montréal, Canada},
state = {published},
author = {Dhingra K{kirti}{Department Physiology of Cognitive Processes}, Mishra A{anuragrk}{Department Physiology of Cognitive Processes}, Engelmann J{joern}{Department High-Field Magnetic Resonance}, Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}, Canals S{canals}, Pohmann R{rolf}{Department High-Field Magnetic Resonance}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Maier ME and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 5311,
title = {Novel Calcium Sensitive MRI Contrast Agent: A Potential Agent for in vivo testing},
year = {2008},
month = {9},
number = {1502},
abstract = {Ca2+ plays an important dual role as a carrier of electrical current and as a second messenger in the brain. Its effects are much more diverse than of other second messengers such as cAMP (3',5'-cyclic adenosine monophosphate) and DAG (Diacylglycerol) as its actions are mediated by large array of proteins including protein kinases. Optical imaging with the help of fluorescent dyes has revealed the important role played by Ca2+; however it is limited by depth penetration and photobleaching side product. Magnetic Resonance Imaging (MRI), owing to its noninvasive characteristics together with its high spatial and temporal resolution doesn’t possess such limitations. In order to exploit these characteristics of MRI, Li. et al. (JACS comm. 1999) have proposed a smart contrast agent based on the high affinity chelator BAPTA, showing sensitivity to Ca2+ concentration in the range of 0.1 to 10 µM with an apparent dissociation constant of 0.96 µM. Contrast agents with such a strong affinity Ca2+ chelator are likely to be saturated once the Ca2+ concentration exceeds 1µM. We report here the synthesis of a Ca2+ sensitive smart contrast agent based on a low affinity chelator APTRA (o-aminophenol-N,N,O-triacetate). The agent showed 100% relaxivity enhancement in presence of Ca2+. Besides its excellent sensitivity, the agent was found Ca2+ selective in the presence of Mg2+ and Zn2+. Its relaxivity response in physiological media such as artificial cerebro-spinal fluid (ACSF) and artificial extracellular matrix (AECM) was found to be 37 % and 27 % respectively. CSF is the fluid that occupies the subarachnoid space and ventricular system around and inside the brain while ECM materials are mostly present in intercellular spaces between neurons and glia. The observed relaxivity changes in these physiological media prove the prospects of the agent for in vivo tests.},
web_url = {http://www.abstractsonline.com/viewer/viewAbstract.asp?CKey={D8AE58D9-C2EA-4152-BA98-1137F8656F49}&MKey={B47BAE74-CCA9-4C27-80FB-0005AFC9E5C0}&AKey={A4C6DD8F-4BF2-400D-97ED-20C14381CDBB}&SKey={EB48FD2C-03BC-414B-8733-3C12AFA98531}},
event_name = {2008 World Molecular Imaging Congress (WMIC)},
event_place = {Nice, France},
state = {published},
author = {Dhingra K{kirti}{Department Physiology of Cognitive Processes}, Maier ME, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Angelovski G{goran}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ CanalsBL2008,
title = {Functional magnetic resonance imaging (fMRI) of synaptic plasticity},
year = {2008},
month = {7},
volume = {6},
number = {079.4},
abstract = {Repetitive stimulation of hippocampal neurons induce a fast and prolonged increase in local synaptic strength, which is known as LTP (long-term potentiation). LTP is currently considered as being the cellular model of associative learning and memory. Despite the relevance of such phenomenon in the healthy and diseased brain, and all valuable information gained in the study of its cellular and molecular mechanisms, little is known about its role in whole-brain functional connectivity. The lack of a better understanding of the context-dependent network organization most likely reflects the fact that most current methodologies are not really suited for the study of mass action. In an attempt to overcome this limitation, we previously combined electrophysiological techniques and electrical microstimulation of the rat perforant path with functional magnetic resonance imaging (fMRI) (Canals et al. 2008, in press) and showed that the fMRI signal (BOLD) in this model is a good surrogate of the neuronal activity as measured electrophysiologically. Here, we investigate the functional patterns produced as a result of long-term potentiation of synaptic transmission in the rat hippocampus. FMRI maps of the entire brain were obtained before, during and after the induction of LTP, demonstrating changes in functional connectivity due to synaptic potentiation. Furthermore, our results demonstrate that the magnitude of the potentiation is heterogeneously distributed across different hippocampal areas, and that interhemispheric communication is also potentiated after LTP induction. The present model (BOLD-LTP) represents the first demonstration of synaptic plasticity using fMRI and will allow us to further study the information transfer between the hippocampus, the cerebral cortex and subcortical structures, providing new data for the understanding of memory and learning processes.},
web_url = {http://fens2008.neurosciences.asso.fr/},
event_name = {6th Forum of European Neuroscience (FENS 2008)},
event_place = {Geneva, Switzerland},
state = {published},
author = {Canals S{canals}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 4616,
title = {In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing},
year = {2007},
month = {5},
volume = {2007},
number = {2464},
pages = {481},
abstract = {One of the main problems in systems biology is to obtain information between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge the applicability of this technique. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. On the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to
produce detectable contrast and reliable connectivity maps.Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps.},
web_url = {http://www.ismrm.org/07/},
event_name = {2007 Joint Annual Meeting ISMRM-ESMRMB},
event_place = {Berlin, Germany},
state = {published},
author = {Canals S{canals}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Keller AL{akeller}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}

@Poster{ 4302,
title = {In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing},
journal = {Neuroforum},
year = {2007},
month = {4},
volume = {13},
number = {Supplement},
pages = {1221},
abstract = {One of the main problems in systems biology is to obtain information on signal processing between
interconnected groups of neurons in highly distributed networks. The recently introduced technique of
manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to
these studies. However, several drawbacks exist that challenge its applicability. High Mn2+ concentrations
produce cytotoxic effects that can perturb the circuits under study. In the other hand, the MR signal is
proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to
produce detectable contrast and reliable connectivity maps.
Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and
extension of the obtained connectivity maps.
The somatosensory cortex of male SD rats was stereotaxically injected with different Mn2+-containing
solutions. Total amount of injected Mn2+ ranged between 1 and 16 nmol and the injected volumes between 10
and 80 nL. Osmolarity and pH effects were investigated injecting pH buffered solutions of Mn2+ (pH 7.3 in
Tris-HCl buffer vs. 5.5 in H2O) at different concentration (0.05, 0.1 and 0.8 M MnCl2). Same amounts of
Mn2+ (8nmol) delivered to the tissue at different infusion rates were also compared. Following the injection,
T1-weighted MR imaging (250 mm isotropic resolution) was performed in a 7T scanner at different time
points. Fifteen days after the injection animals were sacrificed and brains processed for histology. Nissl
staining as well as GFAP and NeuN immunohistochemistry (selective staining for astrocytes and neurons,
respectively) were performed in the brain sections to examine cellular toxicity.
All injections produced connectivity maps consistent with the known anterograde projections of SI cortex
based on classical neuronal tract-tracing techniques. Our results show that pH buffered solution improve the
effectiveness of MEMRI, increasing T1 contrast in the projection sites. In addition, injections of pH buffered
and isotonic solutions of 50 and 100 mM MnCl2 yielded more extensive connectivity maps, in particular, ipsiand
contra-lateral corticocortical connections were evident in all animal injected with those solutions but not
with the more usual MEMRI protocol (0.8M MnCl2 in H2O). Hypertonic and non-buffered solutions
containing 8nmol Mn2+ resulted in neuronal death and astrogliosis in extensive areas around the injection
point. In sharp contrast, no neuronal toxicity was observed with injections containing up to 8nmol of Mn2+ in
isotonic solutions of up to 100 mM MnCl2 and pH 7.3. Slow infusion rates demonstrated also to be
advantageous and permitted application of larger amounts of Mn2+ without toxic effects, resulting in better T1
contrast in the low density projection fields. Any sign of toxicity was observed in any condition in the
projection fields.
We conclude that refined protocols for MEMRI improve the quality and extension of connectivity maps and
preserves tissue viability, assuring the application of this technique in longitudinal experiments.},
file_url = {/fileadmin/user_upload/files/publications/T38-4C_4302[0].pdf},
web_url = {http://www.neuro.uni-goettingen.de/nbc.php?sel=archiv},
event_name = {31st Göttingen Neurobiology Conference},
event_place = {Göttingen, Germany},
state = {published},
author = {Canals S{canals}, Beyerlein M{bayo}{Department Physiology of Cognitive Processes}, Keller AL{akeller}{Department Physiology of Cognitive Processes}, Murayama Y{yusuke}{Department Physiology of Cognitive Processes} and Logothetis NK{nikos}{Department Physiology of Cognitive Processes}}
}