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Your search keyword '"Guillaume P. Dugué"' showing total 10 results
Start Over Author "Guillaume P. Dugué" Topic 0302 clinical medicine
10 results on '"Guillaume P. Dugué"'

1. Inertial Measurement of Head Tilt in Rodents: Principles and Applications to Vestibular Research

Author

Pauline Liaudet, Lionel Reveret, Mathieu Petremann, Romain Fayat, Guillaume P. Dugué, Vincent Descossy, Viviana Delgado Betancourt, Thibault Goyallon, Dugué, Guillaume, 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), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Sensorion [Montpellier], Calcul des Variations, Géométrie, Image (CVGI), Laboratoire Jean Kuntzmann (LJK), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), ANR-20-CE37-0016,InVest,Circuits vestibulo-cérébelleux impliqués dans la cognition spatiale(2020), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, 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), 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 des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris

Subjects
Inertial frame of reference, Computer science, Movement, Acceleration, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, unilateral vestibular lesion, Rodentia, TP1-1185, Biochemistry, Motion capture, Article, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, Inertial measurement unit, [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Animals, Computer vision, Electrical and Electronic Engineering, orientation filters, Instrumentation, 030304 developmental biology, Vestibular system, 0303 health sciences, Quantitative Biology::Neurons and Cognition, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Orientation (computer vision), business.industry, Chemical technology, head tilt, vestibular system, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], inertial sensors, attitude estimation, Atomic and Molecular Physics, and Optics, Rats, Tilt (optics), rodents, Computer Science::Programming Languages, Head (vessel), Vestibule, Labyrinth, Artificial intelligence, business, 030217 neurology & neurosurgery, Gravitation
Abstract

Inertial sensors are increasingly used in rodent research, in particular for estimating head orientation relative to gravity, or head tilt. Despite this growing interest, the accuracy of tilt estimates computed from rodent head inertial data has never been assessed. Using readily available inertial measurement units mounted onto the head of freely moving rats, we benchmarked a set of tilt estimation methods against concurrent 3D optical motion capture. We show that, while low-pass filtered head acceleration signals only provided reliable tilt estimates in static conditions, sensor calibration combined with an appropriate choice of orientation filter and parameters could yield average tilt estimation errors below 1.5∘ during movement. We then illustrate an application of inertial head tilt measurements in a preclinical rat model of unilateral vestibular lesion and propose a set of metrics describing the severity of associated postural and motor symptoms and the time course of recovery. We conclude that headborne inertial sensors are an attractive tool for quantitative rodent behavioral analysis in general and for the study of vestibulo-postural functions in particular.

Published
2021
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2. Optogenetic Tractography for anatomo-functional characterization of cortico-subcortical neural circuits in non-human primates

Author

Caroline Jan, Koichi Hosomi, Emmanuel Brouillet, Christophe Pouzat, Kyriacos A. Mitrophanous, Edward S. Boyden, Xavier Drouot, Philippe Hantraye, J. F. Mangin, Romina Aron-Badin, J. Dauguet, Stéphane Palfi, S Senova, Isabelle Doignon, G. S. Ralph, L. Barnes, Frédéric Pain, Guillaume P. Dugué, C. Poupon, Hannah J Stewart, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Massachusetts Institute of Technology. Media Laboratory, Program in Media Arts and Sciences (Massachusetts Institute of Technology), and Boyden, Edward

Subjects
0301 basic medicine, Male, Deep brain stimulation, medicine.medical_treatment, Genetic Vectors, lcsh:Medicine, Action Potentials, Biology, Optogenetics, Article, 03 medical and health sciences, 0302 clinical medicine, Genes, Reporter, Subthalamic Nucleus, Transduction, Genetic, Biological neural network, medicine, Connectome, Animals, lcsh:Science, [PHYS]Physics [physics], Multidisciplinary, Opsins, lcsh:R, Lentivirus, Motor Cortex, Macaca mulatta, Magnetic Resonance Imaging, Neuromodulation (medicine), Transcranial magnetic stimulation, Subthalamic nucleus, 030104 developmental biology, nervous system, lcsh:Q, Nerve Net, Neuroscience, 030217 neurology & neurosurgery, Tractography
Abstract

Dissecting neural circuitry in non-human primates (NHP) is crucial to identify potential neuromodulation anatomical targets for the treatment of pharmacoresistant neuropsychiatric diseases by electrical neuromodulation. How targets of deep brain stimulation (DBS) and cortical targets of transcranial magnetic stimulation (TMS) compare and might complement one another is an important question. Combining optogenetics and tractography may enable anatomo-functional characterization of large brain cortico-subcortical neural pathways. For the proof-of-concept this approach was used in the NHP brain to characterize the motor cortico-subthalamic pathway (m_CSP) which might be involved in DBS action mechanism in Parkinson’s disease (PD). Rabies-G-pseudotyped and Rabies-G-VSVg-pseudotyped EIAV lentiviral vectors encoding the opsin ChR2 gene were stereotaxically injected into the subthalamic nucleus (STN) and were retrogradely transported to the layer of the motor cortex projecting to STN. A precise anatomical mapping of this pathway was then performed using histology-guided high angular resolution MRI tractography guiding accurately cortical photostimulation of m_CSP origins. Photoexcitation of m_CSP axon terminals or m_CSP cortical origins modified the spikes distribution for photosensitive STN neurons firing rate in non-equivalent ways. Optogenetic tractography might help design preclinical neuromodulation studies in NHP models of neuropsychiatric disease choosing the most appropriate target for the tested hypothesis.

Published
2018
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3. Activity patterns of serotonin neurons underlying cognitive flexibility

Author

Sara Matias, Eran Lottem, Zachary F. Mainen, and Guillaume P. Dugué

Subjects
Dorsal Raphe Nucleus, 0301 basic medicine, Serotonin, Surprise, Mouse, QH301-705.5, media_common.quotation_subject, Perseveration, Science, Reversal Learning, perseveration, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Dopamine, medicine, Animals, Closure (psychology), Biology (General), media_common, General Immunology and Microbiology, General Neuroscience, Cognitive flexibility, Flexibility (personality), Serotonin-dopamine opponency, General Medicine, 030104 developmental biology, Mood, reversal learning, Medicine, medicine.symptom, Psychology, Neuroscience, 030217 neurology & neurosurgery, Serotonergic Neurons, Research Article, medicine.drug
Abstract

Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine–serotonin opponency with potential clinical implications. DOI: http://dx.doi.org/10.7554/eLife.20552.001, eLife digest Serotonin is a molecule that plays various roles in the human body. In the brain, it is involved in regulating mood and emotions. Growing evidence suggests that serotonin also helps animals – including humans – adapt their behavior to changes in their environment. To allow for such behavioral flexibility, serotonin might promote changes in the underlying brain structures and activity. In a type of learning known as ‘reversal learning’, for instance, it is necessary to adapt to a sudden change in a previously familiar environment. For example, if there were a road closure on a person’s way to work, they might want to learn to stop following their usual route and learn a new and better one. Previous research has shown that when serotonin signaling is reduced, people persevere. That is, they will keep following the old route even if it is no longer the best choice. How this process works is still largely unknown. To start unraveling these mechanisms, Matias et al. trained mice in a reversal learning task while manipulating and recording the activity of the neurons that produce serotonin. The results showed that when the activity in serotonin neurons was experimentally blocked, the mice tended to keep looking for a reward that was no longer available. Then, by recording the activity of serotonin neurons, Matias et al. found that it was the surprise of discovering a change in a previously familiar environment that activates serotonin neurons. It did not matter whether the change was better or worse than expected. The findings suggest that together with dopamine, another molecule involved in learning from rewards, serotonin could play an important role during reversal learning. One next step will be to determine if serotonin mainly stops perseverance in its tracks, or whether it works by helping to unlearn the old behavior, or a combination of both. In the future, this could further our understanding of depression, which can be viewed as a disorder characterized by patients being unable to adapt to adverse situations, leaving them trapped to repeat behaviors and thoughts that are not beneficial. Future studies could also build on these findings to guide the development of new treatments for depression that involve serotonin. DOI: http://dx.doi.org/10.7554/eLife.20552.002

Published
2017

4. Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge

Author

Clément Léna, Daniela Popa, Fekrije Selimi, Vanessa Gautheron, Nicolas Guyon, Stéphane Dieudonné, Jean-Christophe Cassel, Frédéric Doussau, Joseph Chaumont, Guillaume P. Dugué, Jean-Luc Dupont, Bernard Poulain, Aline Stephan, Antoine M. Valera, Philippe Isope, Païkan Marcaggi, Michel Barrot, Sophie Reibel-Foisset, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, 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), 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), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme d'hébergement et d'exploration fonctionnelle (Chronobiotron), Laboratoire de neurosciences cognitives et adaptatives (LNCA), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cerebellum, Purkinje cell, Mice, Transgenic, Cerebellar Purkinje cell, Olivary Nucleus, Biology, Optogenetics, Deep cerebellar nuclei, Efferent Pathways, Mice, Purkinje Cells, 03 medical and health sciences, 0302 clinical medicine, Channelrhodopsins, motor control, medicine, Animals, olivo-cerebellar loop, 030304 developmental biology, 0303 health sciences, Multidisciplinary, complex spikes, Climbing fiber, Biological Sciences, Immunohistochemistry, medicine.anatomical_structure, nervous system, Rotarod Performance Test, Cerebellar cortex, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Motor learning, Neuroscience, 030217 neurology & neurosurgery
Abstract

Climbing fibers, the projections from the inferior olive to the cerebellar cortex, carry sensorimotor error and clock signals that trigger motor learning by controlling cerebellar Purkinje cell synaptic plasticity and discharge. Purkinje cells target the deep cerebellar nuclei, which are the output of the cerebellum and include an inhibitory GABAergic projection to the inferior olive. This pathway identifies a potential closed loop in the olivo-cortico-nuclear network. Therefore, sets of Purkinje cells may phasically control their own climbing fiber afferents. Here, using in vitro and in vivo recordings, we describe a genetically modified mouse model that allows the specific optogenetic control of Purkinje cell discharge. Tetrode recordings in the cerebellar nuclei demonstrate that focal stimulations of Purkinje cells strongly inhibit spatially restricted sets of cerebellar nuclear neurons. Strikingly, such stimulations trigger delayed climbing-fiber input signals in the stimulated Purkinje cells. Therefore, our results demonstrate that Purkinje cells phasically control the discharge of their own olivary afferents and thus might participate in the regulation of cerebellar motor learning.

Published
2013
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5. 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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6. Electrical Coupling Mediates Tunable Low-Frequency Oscillations and Resonance in the Cerebellar Golgi Cell Network

Author

Guillaume P. Dugué, Stéphane Dieudonné, Mireille Chat, Eric J. Schwartz, Clément Léna, Maxime Lévesque, Nicolas Brunel, Richard Courtemanche, and Vincent Hakim

Subjects
Periodicity, Patch-Clamp Techniques, Neuroscience(all), Models, Neurological, Population, Action Potentials, Mice, Transgenic, Biology, Membrane Potentials, Mice, 03 medical and health sciences, symbols.namesake, Electrical Synapses, 0302 clinical medicine, Rhythmic inhibition, Interneurons, Golgi cell, Cerebellum, Excitatory Amino Acid Agonists, medicine, Animals, education, 030304 developmental biology, Neurons, 0303 health sciences, education.field_of_study, Kainic Acid, General Neuroscience, Afterhyperpolarization, Golgi apparatus, Mice, Inbred C57BL, medicine.anatomical_structure, nervous system, Cerebellar cortex, Excitatory postsynaptic potential, symbols, Nerve Net, Neuroscience, 030217 neurology & neurosurgery
Abstract

SummaryTonic motor control involves oscillatory synchronization of activity at low frequency (5–30 Hz) throughout the sensorimotor system, including cerebellar areas. We investigated the mechanisms underpinning cerebellar oscillations. We found that Golgi interneurons, which gate information transfer in the cerebellar cortex input layer, are extensively coupled through electrical synapses. When depolarized in vitro, these neurons displayed low-frequency oscillatory synchronization, imposing rhythmic inhibition onto granule cells. Combining experiments and modeling, we show that electrical transmission of the spike afterhyperpolarization is the essential component for oscillatory population synchronization. Rhythmic firing arises in spite of strong heterogeneities, is frequency tuned by the mean excitatory input to Golgi cells, and displays pronounced resonance when the modeled network is driven by oscillating inputs. In vivo, unitary Golgi cell activity was found to synchronize with low-frequency LFP oscillations occurring during quiet waking. These results suggest a major role for Golgi cells in coordinating cerebellar sensorimotor integration during oscillatory interactions.

Published
2009
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7. 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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8. Optogenetic Recruitment of Dorsal Raphe Serotonergic Neurons Acutely Decreases Mechanosensory Responsivity in Behaving Mice

Author

Eran Lottem, Magor L. Lorincz, Sara Matias, Zachary F. Mainen, Enrica Audero, Guillaume P. Dugué, Patrícia A. Correia, and Clément Léna

Subjects
Dorsal Raphe Nucleus, Serotonin, Neurophysiology, lcsh:Medicine, Stimulation, Mice, Transgenic, Biology, Optogenetics, Serotonergic, Mechanotransduction, Cellular, Biochemistry, Photostimulation, 03 medical and health sciences, Mice, 0302 clinical medicine, Dorsal raphe nucleus, Organ Culture Techniques, Animals, Tactile Sensation, lcsh:Science, 030304 developmental biology, Neurons, 0303 health sciences, 8-Hydroxy-2-(di-n-propylamino)tetralin, Multidisciplinary, Raphe, Behavior, Animal, Neuromodulation, lcsh:R, Biology and Life Sciences, Pain Sensation, Neurochemistry, Anatomy, Serotonin 5-HT1 Receptor Agonists, Sensory Systems, Somatosensory System, nervous system, Autoreceptor, lcsh:Q, Neuroscience, 030217 neurology & neurosurgery, Photic Stimulation, Research Article
Abstract

The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses. ERC 250334, 5-HT Optogenetic MSCA 220098 info:eu-repo/semantics/publishedVersion

Published
2014

9. Balanced activity in basal ganglia projection pathways is critical for contraversive movements

Author

Guillaume P. Dugué, Rui M. Costa, Zachary F. Mainen, Fatuel Tecuapetla, and Sara Matias

Subjects
Male, Movement, General Physics and Astronomy, Mice, Transgenic, Striatum, Optogenetics, Biology, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Neuron types, Basal Ganglia, Functional Laterality, Article, 03 medical and health sciences, 0302 clinical medicine, Basal ganglia, Neural Pathways, Animals, 10. No inequality, Projection (set theory), 030304 developmental biology, 0303 health sciences, Multidisciplinary, General Chemistry, Mice, Inbred C57BL, Neuroscience, 030217 neurology & neurosurgery
Abstract

The basal ganglia, and the striatum in particular, have been implicated in the generation of contraversive movements. The striatum projects to downstream basal ganglia nuclei through two main circuits, originating in striatonigral and striatopallidal neurons, and different models postulate that the two pathways can work in opposition or synergistically. Here we show striatonigral and striatopallidal neurons are concurrently active during spontaneous contraversive movements. Furthermore, we show that unilateral optogenetic inhibition of either or both projection pathways disrupts contraversive movements. Consistently, simultaneous activation of both neuron types produces contraversive movements. Still, we also show that imbalanced activity between the pathways can result in opposing movements being driven by each projection pathway. These data show that balanced activity in both striatal projection pathways is critical for the generation of contraversive movements and highlights that imbalanced activity between the two projection pathways can result in opposing motor output., The striatum is required for evoking contraversive movements from each brain hemisphere, but it is unclear how. Here, Tecuapetla et al. use optogenetics to inhibit direct and indirect downstream striatal projection pathways, and show that activity in both pathways is necessary for contraversive movements.

Published
2014

10. 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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