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7 results on '"Charly V. Rousseau"'

1. A deep learning algorithm for 3D cell detection in whole mouse brain image datasets

Author

Charly V. Rousseau, Troy W. Margrie, Christian J. Niedworok, Sepiedeh Keshavarzi, Molly Strom, Lee Cossell, Adam L. Tyson, Chryssanthi Tsitoura, University College of London [London] (UCL), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Nervous system, Rodent, Computer science, Cell, Datasets as Topic, Viral infection, Tissue Preparation, Machine Learning, Mice, Open Science, 0302 clinical medicine, Animal Cells, Microscopy, Biology (General), Neurons, 0303 health sciences, Ecology, Artificial neural network, biology, Applied Mathematics, Simulation and Modeling, Brain, Software Engineering, Fluorescence, medicine.anatomical_structure, Computational Theory and Mathematics, Fully automated, Modeling and Simulation, Physical Sciences, Engineering and Technology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cellular Types, Algorithm, Algorithms, Open Source Software, Research Article, Computer and Information Sciences, Neural Networks, Imaging Techniques, Science Policy, QH301-705.5, Neuroimaging, Image Analysis, Research and Analysis Methods, Image (mathematics), Computer Software, Cellular and Molecular Neuroscience, 03 medical and health sciences, Deep Learning, Artificial Intelligence, biology.animal, Genetics, medicine, Animals, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Neuronal somata, business.industry, Deep learning, Biology and Life Sciences, Cell Biology, 030104 developmental biology, Cytoplasm, Cellular Neuroscience, Artificial intelligence, business, Mathematics, 030217 neurology & neurosurgery, Neuroscience
Abstract

Understanding the function of the nervous system necessitates mapping the spatial distributions of its constituent cells defined by function, anatomy or gene expression. Recently, developments in tissue preparation and microscopy allow cellular populations to be imaged throughout the entire rodent brain. However, mapping these neurons manually is prone to bias and is often impractically time consuming. Here we present an open-source algorithm for fully automated 3D detection of neuronal somata in mouse whole-brain microscopy images using standard desktop computer hardware. We demonstrate the applicability and power of our approach by mapping the brain-wide locations of large populations of cells labeled with cytoplasmic fluorescent proteins expressed via retrograde trans-synaptic viral infection., Author summary Mapping cells in the brain is a key method in neuroscience, and was traditionally carried out on manually prepared thin sections. Today, modern microscopy approaches allow the entire mouse brain to be imaged in 3D at high resolution. Due to their often complex somatic morphology, detecting cytoplasmically labelled neurons in these large image datasets is highly challenging compared, for example, to detecting spherical cell nuclei. Additionally, a neuron can often be mistakenly detected multiple times, or two cells can be interpreted as a single cell. Here we have developed a freely available algorithm for detecting cytoplasmically labelled neuronal somata in these images which can be run faster than the data can be acquired, and without the bias of manual analysis. The ability to quickly map cellular distributions throughout the mouse brain will lead to a greater understanding of both its structure and function. As with flies, nematodes and fish, detecting and mapping cells in 3D throughout the entire mammalian brain will allow for new experiments designed to understand the structural basis of its myriad complex functions.

Published
2021
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2. Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula

Author

Stéphane Dieudonné, Charly V. Rousseau, Pierre Paoletti, Cendra Agulhon, Teddy Grand, Marco A. Diana, Yo Otsu, Eric J Schwartz, T. Bessaih, S. Abi Gerges, Brigitte L. Kieffer, Ferenc Mátyás, K. Pietrajtis, László Acsády, Emmanuel Darcq, Gestionnaire, Hal Sorbonne Université, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), McGill University Health Center [Montreal] (MUHC), Sorbonne Université (SU), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hungarian Academy of Sciences (MTA), Centre Neurosciences intégratives et Cognition (INCC - UMR 8002), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry [Montreal, QC, Canada] (Faculty of Medicine), McGill University-Douglas Hospital Research Center [Montreal, QC, Canada], Laboratory of Thalamus Research [Budapest, Hungary] (Institute of Experimental Medicine), Research Centre for Natural Sciences, Department of Anatomy and Histology [Budapest, Hungary], University of Veterinary Medicine [Budapest, Hungary], This study was supported by fellowships (NKTH-)ANR-09-BLAN-0401 to S.D., M.A.D., and L.A., and ANR-17-CE16-0014 to P.P., S.D., B.L.K., and M.A.D., by Emergence Sorbonne (S17JRSU003) and CNRS (PICS 7415) to M.A.D., by the European Research Council (693021) to P.P., by ERC-FRONTHAL (742595) to L.A., by grants FK124434 and 2017-1.2.1-NKP-2017-00002 to F.M., and by the National Institute of Drug Abuse (05010) and the National Institute on Alcohol Abuse and Alcoholism (16658) to B.L.K. C.V.R. was supported by FRM grant FDT20100919977. C.A. was supported by a Paris School of Neuroscience 'Chair of Excellence' award and by a NARSAD Y.I. Award., ANR-17-CE16-0014,GluBrain3A,Role des récepteurs NMDA contenant la sous-unité atypique GluN3A dans la physiologie du cerveau adulte(2017), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Patch-Clamp Techniques, Protein subunit, [SDV]Life Sciences [q-bio], Emotions, Glycine, Nerve Tissue Proteins, Receptors, N-Methyl-D-Aspartate, Article, Cell Line, 03 medical and health sciences, Mice, [SCCO]Cognitive science, 0302 clinical medicine, Conditioning, Psychological, Premovement neuronal activity, Animals, Humans, Patch clamp, Receptor, Glycine receptor, 030304 developmental biology, Mice, Knockout, Neurons, 0303 health sciences, Habenula, Multidisciplinary, Behavior, Animal, Chemistry, [SCCO.NEUR]Cognitive science/Neuroscience, 3. Good health, [SDV] Life Sciences [q-bio], Excitatory postsynaptic potential, NMDA receptor, Calcium, Cues, Neuroscience, Neuroglia, 030217 neurology & neurosurgery
Abstract

An inhibitor causes neuronal excitation Glycine is thought to be primarily an inhibitory neurotransmitter. However, it also acts as a coagonist on excitatory N -methyl-D-aspartate (NMDA) receptors. Otsu et al. examined the function of the NMDA receptor subunit combination GluN1/GluN3A in the medial habenula (MHb) of adult mice. This NMDA receptor subunit combination in MHb neurons is activated by glycine released from astrocytes. Activation of GluN1/GluN3A NMDA receptors causes depolarization and increased spiking of MHb neurons. Reducing GluN3A receptor subunit levels in the MHb blocks conditioned place aversion. Science , this issue p. 250

Published
2019
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3. The Stimulus Selectivity and Connectivity of Layer Six Principal Cells Reveals Cortical Microcircuits Underlying Visual Processing

Author

Molly Strom, Charly V. Rousseau, Mateo Vélez-Fort, Ian R. Wickersham, Christian J. Niedworok, Troy W. Margrie, Alexander Brown, and Ede A. Rancz

Subjects
Patch-Clamp Techniques, Visual perception, Neuroscience(all), Sensory system, Stimulus (physiology), Visual system, Somatosensory system, Article, Visual processing, Mice, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, Image Processing, Computer-Assisted, medicine, Animals, Visual Pathways, Visual Cortex, 030304 developmental biology, 0303 health sciences, Neocortex, General Neuroscience, Mice, Inbred C57BL, Visual cortex, medicine.anatomical_structure, Visual Perception, Psychology, Neuroscience, Photic Stimulation, 030217 neurology & neurosurgery
Abstract

SummarySensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network.

Published
2014
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4. NMDA Receptors with Incomplete Mg2+Block Enable Low-Frequency Transmission through the Cerebellar Cortex

Author

Jason S. Rothman, Charly V. Rousseau, Marco Diana, Eric J. Schwartz, Robin Angus Silver, Guillaume P. Dugué, Stéphane Dieudonné, Réseaux de neurones et rythmes physiopathologiques = Neuronal Networks and Physiopathological Rhythms (NPS-09), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CNRS, INSERM, Agence Nationale de la Recherche/Biotechnology and Biological Sciences Research Council [2007 BSYS 010, F005490], Wellcome Trust [064413, 095667], European Research Council, Marie Curie Actions International Incoming Fellowship [MIF-CT-2006-040118], Fondation pour la Recherche Medicale [SPF20081214925], Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Glycine, Action Potentials, AMPA receptor, In Vitro Techniques, Biology, Neurotransmission, Receptors, N-Methyl-D-Aspartate, Synaptic Transmission, Article, Cerebellar Cortex, Purkinje Cells, 03 medical and health sciences, Nerve Fibers, 0302 clinical medicine, Animals, Magnesium, Rats, Wistar, 030304 developmental biology, Neurons, 0303 health sciences, General Neuroscience, Excitatory Postsynaptic Potentials, Depolarization, Resorcinols, Resting potential, Rats, nervous system, Metabotropic glutamate receptor, Cerebellar cortex, Excitatory postsynaptic potential, NMDA receptor, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery
Abstract

The cerebellar cortex coordinates movements and maintains balance by modifying motor commands as a function of sensory-motor context, which is encoded by mossy fiber (MF) activity. MFs exhibit a wide range of activity, from brief precisely timed high-frequency bursts, which encode discrete variables such as whisker stimulation, to low-frequency sustained rate-coded modulation, which encodes continuous variables such as head velocity. While high-frequency MF inputs have been shown to activate granule cells (GCs) effectively, much less is known about sustained low-frequency signaling through the GC layer, which is impeded by a hyperpolarized resting potential and strong GABAA-mediated tonic inhibition of GCs. Here we have exploited the intrinsic MF network of unipolar brush cells to activate GCs with sustained low-frequency asynchronous MF inputs in rat cerebellar slices. We find that low-frequency MF input modulates the intrinsic firing of Purkinje cells, and that this signal transmission through the GC layer requires synaptic activation of Mg2+-block-resistant NMDA receptors (NMDARs) that are likely to contain the GluN2C subunit. Slow NMDAR conductances sum temporally to contribute approximately half the MF-GC synaptic charge at hyperpolarized potentials. Simulations of synaptic integration in GCs show that the NMDAR and slow spillover-activated AMPA receptor (AMPAR) components depolarize GCs to a similar extent. Moreover, their combined depolarizing effect enables the fast quantal AMPAR component to trigger action potentials at low MF input frequencies. Our results suggest that the weak Mg2+block of GluN2C-containing NMDARs enables transmission of low-frequency MF signals through the input layer of the cerebellar cortex.

Published
2012
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5. A Circuit for Integration of Head- and Visual-Motion Signals in Layer 6 of Mouse Primary Visual Cortex

Author

Lee Cossell, Troy W. Margrie, Sepiedeh Keshavarzi, Stephen C. Lenzi, Mateo Vélez-Fort, Charly V. Rousseau, Molly Strom, and Edward F. Bracey

Subjects
Male, 0301 basic medicine, Visual perception, genetic structures, Computer science, Nerve net, Motion Perception, Mice, Transgenic, Angular velocity, Visual system, Article, 2P imaging, mouse primary visual cortex, Mice, 03 medical and health sciences, 0302 clinical medicine, Retrosplenial cortex, medicine, Animals, Visual Pathways, head-velocity signals, Motion perception, Visual Cortex, Vestibular system, go/no go task, General Neuroscience, Bayesian approach, whole-cell patch clamp, layer 6 neurons, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Visual cortex, Neuropixels dense silicon probe, Head Movements, egocentric framework, Female, Nerve Net, Neuroscience, Photic Stimulation, 030217 neurology & neurosurgery
Abstract

Summary To interpret visual-motion events, the underlying computation must involve internal reference to the motion status of the observer’s head. We show here that layer 6 (L6) principal neurons in mouse primary visual cortex (V1) receive a diffuse, vestibular-mediated synaptic input that signals the angular velocity of horizontal rotation. Behavioral and theoretical experiments indicate that these inputs, distributed over a network of 100 L6 neurons, provide both a reliable estimate and, therefore, physiological separation of head-velocity signals. During head rotation in the presence of visual stimuli, L6 neurons exhibit postsynaptic responses that approximate the arithmetic sum of the vestibular and visual-motion response. Functional input mapping reveals that these internal motion signals arrive into L6 via a direct projection from the retrosplenial cortex. We therefore propose that visual-motion processing in V1 L6 is multisensory and contextually dependent on the motion status of the animal’s head., Highlights • Inputs onto V1 L6 neurons convey head-motion information • These L6 signals are widespread and provide a reliable estimate of angular velocity • In L6 neurons, vestibular and visual inputs sum during sensory processing • At least in part, V1 L6 head-motion signals are conveyed via an RSP-V1 pathway, V1 layer 6 neurons receive a widespread head-motion signal that is integrated with visual input during visual-motion processing. These V1 head-motion inputs project from the retrosplenial cortex, a multisensory area involved in spatial navigation and contextual processing.

Published
2018
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6. A subcortical inhibitory signal for behavioral arrest in the thalamus

Author

Charly V. Rousseau, Marco A. Diana, Stéphane Dieudonné, Viktor M. Plattner, Balázs Hangya, Hanns Ulrich Zeilhofer, Guillaume P. Dugué, Kristóf Giber, Hajnalka Bokor, László Havas, László Acsády, Hendrik Wildner, Zsófia Maglóczky, Réseaux de neurones et rythmes physiopathologiques = Neuronal Networks and Physiopathological Rhythms (NPS-09), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Hungarian Scientific Research Fund (OTKA) [T109754, T75676], National Office for Research and Technology [NKTH-ANR-09-BLAN-0401], Research University, Swartz Foundation, EU, Hungarian Korean Joint Laboratory Program, Hungarian Brain Research Program [KTIA\₁3_NAP-A-I/1], Wellcome Trust [fWT094513], Advanced Investigator ERC [DHISP 250128], CNRS, INSERM, Ecole Normale Superieure, French Government and implemented by the ANR [ANR-10LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSL], Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, Acsády, László, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Patch-Clamp Techniques, Thalamus, Glycine, Pontine Tegmentum, 10050 Institute of Pharmacology and Toxicology, 610 Medicine & health, Biology, Inhibitory postsynaptic potential, Article, Mice, 03 medical and health sciences, Nerve Fibers, Receptors, Glycine, 0302 clinical medicine, Receptors, GABA, medicine, Biological neural network, Tegmentum, Animals, GABAergic Neurons, 030304 developmental biology, Afferent Pathways, 0303 health sciences, Behavior, Animal, Intralaminar Thalamic Nuclei, General Neuroscience, 2800 General Neuroscience, Neural Inhibition, Paramedian pontine reticular formation, Optogenetics, medicine.anatomical_structure, nervous system, Forebrain, GABAergic, 570 Life sciences, biology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Brainstem, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Organization of behavior requires rapid coordination of brainstem and forebrain activity. The exact mechanisms of effective communication between these regions are presently unclear. The intralaminar thalamic nuclei (IL) probably serves as a central hub in this circuit by connecting the critical brainstem and forebrain areas. We found that GABAergic and glycinergic fibers ascending from the pontine reticular formation (PRF) of the brainstem evoked fast and reliable inhibition in the IL via large, multisynaptic terminals. This inhibition was fine-tuned through heterogeneous GABAergic and glycinergic receptor ratios expressed at individual synapses. Optogenetic activation of PRF axons in the IL of freely moving mice led to behavioral arrest and transient interruption of awake cortical activity. An afferent system with comparable morphological features was also found in the human IL. These data reveal an evolutionarily conserved ascending system that gates forebrain activity through fast and powerful synaptic inhibition of the IL.

Published
2015
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7. Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Author

Marco Diana, Stéphane Dieudonné, Enrico Mugnaini, Charly V. Rousseau, Andréa Dumoulin, Guillaume P. Dugué, Réseaux de neurones et rythmes physiopathologiques = Neuronal Networks and Physiopathological Rhythms (NPS-09), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Region iie de France and Fondation pour la Recherche Medicale fellowships, French Research Ministry, and Agence Nationale de la Recherche Grant Vesticode [07BSYS010], Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Mossy fiber (hippocampus), Glycine, Glutamic Acid, In Vitro Techniques, Biology, Receptors, Metabotropic Glutamate, Inhibitory postsynaptic potential, Synaptic Transmission, GABA Antagonists, 03 medical and health sciences, Glutamatergic, Nerve Fibers, Receptors, Glycine, 0302 clinical medicine, Interneurons, Postsynaptic potential, Cerebellum, Excitatory Amino Acid Agonists, Animals, Rats, Wistar, GABA Agonists, gamma-Aminobutyric Acid, 030304 developmental biology, Neurons, 0303 health sciences, Kainic Acid, General Neuroscience, fungi, Glycine Agents, Neural Inhibition, Articles, Rats, Inhibitory Postsynaptic Potentials, Metabotropic glutamate receptor, Excitatory postsynaptic potential, GABAergic, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Glutamatergic synapse, Excitatory Amino Acid Antagonists, Neuroscience, 030217 neurology & neurosurgery
Abstract

Inhibitory synapses display a great diversity through varying combinations of presynaptic GABA and glycine release and postsynaptic expression of GABA and glycine receptor subtypes. We hypothesized that increased flexibility offered by this dual transmitter system might serve to tune the inhibitory phenotype to the properties of afferent excitatory synaptic inputs in individual cells. Vestibulocerebellar unipolar brush cells (UBC) receive a single glutamatergic synapse from a mossy fiber (MF), which makes them an ideal model to study excitatory–inhibitory interactions. We examined the functional phenotypes of mixed inhibitory synapses formed by Golgi interneurons onto UBCs in rat slices. We show that glycinergic IPSCs are present in all cells. An additional GABAergic component of large amplitude is only detected in a subpopulation of UBCs. This GABAergic phenotype is strictly anti-correlated with the expression of type II, but not type I, metabotropic glutamate receptors (mGluRs) at the MF synapse. Immunohistochemical stainings and agonist applications show that global UBC expression of glycine and GABAAreceptors matches the pharmacological profile of IPSCs. Paired recordings of Golgi cells and UBCs confirm the postsynaptic origin of the inhibitory phenotype, including the slow kinetics of glycinergic components. These results strongly suggest the presence of a functional coregulation of excitatory and inhibitory phenotypes at the single-cell level. We propose that slow glycinergic IPSCs may provide an inhibitory tone, setting the gain of the MF to UBC relay, whereas large and fast GABAergic IPSCs may in addition control spike timing in mGluRII-negative UBCs.

Published
2012
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