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Activity-dependent functional and structural plasticity in the somatosensory cortex in vivo

English title Activity-dependent functional and structural plasticity in the somatosensory cortex in vivo
Applicant Holtmaat Anthony
Number 153448
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2014 - 31.03.2017
Approved amount 525'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Cellular Biology, Cytology

Keywords (6)

barrel cortex; 2-photon microscopy; long-term potentiation; experience-dependent plasticity; synaptic plasticity; dendritic spines

Lay Summary (French)

Lead
Plasticité structurelle et fonctionnelle dépendant de l'activité dans le cortex somatosensoriel, in vivo
Lay summary

Quand une personne apprend, elle associe une expérience sensorielle avec d'autres stimuli ou avec un comportement particulier.

Les neurones qui sont impliqués dans cet apprentissage ont la capacité de modifier leur connections synaptiques. Ce processus optimise vraisemblablement un traitement ultérieur de la même information et facilite la prévision des conséquences de cette stimulation pour l'individu. Ce type de changement synaptique est appelé plasticité Hebienne. Elle implique que des neurones qui sont activés ensemble sont synaptiquement connectés ensemble.

Nous avons récemment caractérisé, in vivo, différentes formes de plasticité Hebienne qui impliquent des changements synaptiques induits par une stimulation sensorielle.

Dans le présent projet de recherche, nous proposons de continuer à étudier ces mécanismes. Pour ce faire, nous allons utiliser des approches génétiques qui permettent de contrôler l'activité neuronale grâce à des stimulations optiques. Cela va nous permettre d'activer, à distance, des entrées synaptiques spécifiques et de les combiner avec une stimulation sensorielle. En effet, au sein du laboratoire, nous utilisons déjà des techniques d'électrophysiologie et de microscopie qui nous permettent de mesurer la force des synapses qui sont situées dans une région du cerveau de souris qui a pour rôle  de traiter l'information sensorielle venant des moustaches.

Ainsi, nous pensons observer qu'une activation combinée de différentes voies synaptiques aboutit à un renforcement des connexions synaptiques et a pour effet de renforcer l'association entre des entrées sensorielles venant de la moustache avec d'autres entrées synaptiques.

Ces nouvelles découvertes vont avoir pour conséquence d'aider à développer de nouvelles stratégies thérapeutiques  pour le traitement de lésions traumatiques au cerveau mais aussi pour le traitement de maladies neurodégénératives, caractérisées par une perte des entrées synaptiques.
Direct link to Lay Summary Last update: 16.04.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue
Voigt Fabian F., Kirschenbaum Daniel, Platonova Evgenia, Pagès Stéphane, Campbell Robert A. A., Kastli Rahel, Schaettin Martina, Egolf Ladan, van der Bourg Alexander, Bethge Philipp, Haenraets Karen, Frézel Noémie, Topilko Thomas, Perin Paola, Hillier Daniel, Hildebrand Sven, Schueth Anna, Roebroeck Alard, Roska Botond, Stoeckli Esther T., Pizzala Roberto, Renier Nicolas, Zeilhofer Hanns Ulrich, Karayannis Theofanis, et al. (2019), The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue, in Nature Methods, 16(11), 1105-1108.
Higher-Order Thalamocortical Inputs Gate Synaptic Long-Term Potentiation via Disinhibition
Williams Leena E., Holtmaat Anthony (2019), Higher-Order Thalamocortical Inputs Gate Synaptic Long-Term Potentiation via Disinhibition, in Neuron, 101(1), 91-102.e4.
Neurogliaform cortical interneurons derive from cells in the preoptic area
Niquille Mathieu, Limoni Greta, Markopoulos Foivos, Cadilhac Christelle, Prados Julien, Holtmaat Anthony, Dayer Alexandre (2018), Neurogliaform cortical interneurons derive from cells in the preoptic area, in eLife, 7, e32017.
Control of synaptic plasticity in deep cortical networks
Roelfsema Pieter R., Holtmaat Anthony (2018), Control of synaptic plasticity in deep cortical networks, in Nature Reviews Neuroscience, 19(3), 166-180.
Computer assisted detection of axonal bouton structural plasticity in in vivo time-lapse images
Gala Rohan, Lebrecht Daniel, Sahlender Daniela A, Jorstad Anne, Knott Graham, Holtmaat Anthony, Stepanyants Armen (2017), Computer assisted detection of axonal bouton structural plasticity in in vivo time-lapse images, in eLife, 6, e29315.
New recipes with CaMPARI for 'snapshots' of synaptic circuit activity.
Chéreau R Holtmaat A (2017), New recipes with CaMPARI for 'snapshots' of synaptic circuit activity., in J Physiol, 595, 1435.
Structural plasticity and cortical connectivity
Kehayas V and Holtmaat A (2017), Structural plasticity and cortical connectivity, Elsevier, London.
Transcriptomic and anatomic parcellation of 5-HT3AR expressing cortical interneuron subtypes revealed by single-cell RNA sequencing
Frazer S Prados J Niquille M Cadilhac C Markopoulos F Gomez L Tomasello U Telley L Holtmaat (2017), Transcriptomic and anatomic parcellation of 5-HT3AR expressing cortical interneuron subtypes revealed by single-cell RNA sequencing, in Nat Commun, 8, 14219.
Dendrites In Vitro and In Vivo Contain Microtubules of Opposite Polarity and Axon Formation Correlates with Uniform Plus-End-Out Microtubule Orientation
Yau KW Schätzle P Tortosa E Pagès S Holtmaat A Kapitein LC Hoogenraad CC (2016), Dendrites In Vitro and In Vivo Contain Microtubules of Opposite Polarity and Axon Formation Correlates with Uniform Plus-End-Out Microtubule Orientation, in J Neurosci, 36, 1071.
Functional and structural underpinnings of neuronal assembly formation in learning
Holtmaat A Caroni P (2016), Functional and structural underpinnings of neuronal assembly formation in learning, in Nat Neurosci, 19, 1553.
Dissonant Synapses Shall Be Punished
Kehayas V Holtmaat A (2015), Dissonant Synapses Shall Be Punished, in Neuron, 87, 245.
Single cell electroporation for longitudinal imag- ing of synaptic structure and function in the adult mouse neocortex in vivo
Pagès S Cane M Randall J Capello L Holtmaat A (2015), Single cell electroporation for longitudinal imag- ing of synaptic structure and function in the adult mouse neocortex in vivo, in Front Neuroanat, 9, 36.
Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability
Bernardinelli Y Randall J Janett E Nikonenko I König S Jones EV Flores CE Murai KK Bochet CG (2014), Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability, in Curr Biol, 24, 1679.
Correlative in vivo 2-photon imaging and focused ion beam scanning electron microscopy: 3D analysis of neuronal ultrastructure
Maco B Holtmaat A Jorstad A Fua P Knott GW (2014), Correlative in vivo 2-photon imaging and focused ion beam scanning electron microscopy: 3D analysis of neuronal ultrastructure, in Methods Cell Biol, 124, 339.
Modality-specific thalamocortical inputs instruct the identity of postsynaptic L4 neurons
Pouchelon G Gambino F Bellone C Telley L Vitali I Lüscher C Holtmaat A Jabaudon D (2014), Modality-specific thalamocortical inputs instruct the identity of postsynaptic L4 neurons, in Nature, 511, 471.
Sensory-evoked LTP driven by dendritic plateau potentials in vivo
Gambino F Pagès S Kehayas V Baptista D Tatti R Carleton A Holtmaat A (2014), Sensory-evoked LTP driven by dendritic plateau potentials in vivo, in Nature, 515, 116.
Reconstructing Evolving Tree Structures in Time Lapse Sequences by Enforcing Time-Consistency.
Glowacki P Pinheiro MA Mosinska A Turetken E Lebrecht D Holtmaat A Sznitman R Kybic J Fua P, Reconstructing Evolving Tree Structures in Time Lapse Sequences by Enforcing Time-Consistency., in IEEE Trans Pattern Anal Mach Intell.

Collaboration

Group / person Country
Types of collaboration
Graham Knott at the EPFL, Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Pascal Fua at EPFL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Daniel Huber at UNIGE, Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Armen Stepanyants at Northeastern Univeristy United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Brain and Mind Institute winter symposium: Connectivity and Plasticity of Neural Circuits Poster Channelrhodopsin-assisted cortical circuit mapping in vivo 12.12.2016 Lausanne, Switzerland Chéreau Ronan;
Brain and Mind Institute winter symposium: Connectivity and Plasticity of Neural Circuits Talk given at a conference Synaptic plasticity in the mouse somatosensory cortex driven by paralemniscal pathways 12.12.2016 Lausanne, Switzerland Holtmaat Anthony;
Brain and Mind Institute winter symposium: connectivity and plasticity of neural circuits Poster LTP in the mouse barrel cortex driven by cooperative lemniscal and paralemniscal pathway activity 12.12.2016 Lausanne, Switzerland Williams Leena;
Society for Neuroscience 46th annual meeting Poster LTP in the mouse barrel cortex driven by cooperative lemniscal and paralemniscal pathway activity 12.11.2016 San Diego, United States of America Williams Leena;
Probing Neural Networks with Light: Imaging Structure & Function in the Living Brain Talk given at a conference Synaptic plasticity in the mouse somatosensory cortex driven by paralemniscal pathways 21.10.2016 Suzhou, China Holtmaat Anthony;
3rd Bordeaux Neurocampus Conference Talk given at a conference Mechanisms for synaptic plasticity in the mouse somatosensory cortex 28.09.2016 Bordeaux, France Holtmaat Anthony;
10th FENS Forum of Neuroscience Talk given at a conference Local dendritic activity drives plasticity in adult cortical neurons in vivo 02.07.2016 Copenhagen, Denmark Holtmaat Anthony;
Jacques Monod Conference on Optical Imaging of Brain Connectivity: from Synapses to Networks in Action Talk given at a conference Neuronal circuits in the mammalian neocortex 13.06.2016 Roscoff, France Holtmaat Anthony;
Barrel Cortex Function Meeting Talk given at a conference Mechanisms for functional and structural plasticity 19.05.2016 Amsterdam, Netherlands Holtmaat Anthony;
Workshop COSYNE Talk given at a conference Mechanisms for LTP in the mouse barrel cortex. 29.02.2016 Snowbird, United States of America Holtmaat Anthony;
Society for Neuroscience 45th annual meeting Poster Spine outgrowth and stabilization on cortical pyramidal dendrites correlates with the presence of shaft synapses 17.10.2015 Chicago, United States of America Kechagias Vasileios;
Society for Neuroscience 45th annual meeting Poster Anatomical correlates of perceptual learning in mouse barrel cortex 17.10.2015 Chicago, United States of America Lebrecht Daniel;
Workshop COSYNE Talk given at a conference Modes of structural plasticity in somatosensory cortex in vivo 09.03.2015 Snowbird, United States of America Holtmaat Anthony;


Awards

Title Year
Research Prize of the Swiss Brain League 2016

Associated projects

Number Title Start Funding scheme
173125 The role of paralemniscal circuits in cortical plasticity and perception 01.10.2017 Project funding (Div. I-III)
135631 Long-term potentiation and the modification of synaptic structures in vivo 01.04.2011 Project funding (Div. I-III)
173125 The role of paralemniscal circuits in cortical plasticity and perception 01.10.2017 Project funding (Div. I-III)
127289 Structure, Function and Plasticity of the Barrel Cortex 01.01.2010 Sinergia
120685 Experience-dependent structural plasticity of synapses in vivo 01.04.2008 Project funding (Div. I-III)
120685 Experience-dependent structural plasticity of synapses in vivo 01.04.2008 Project funding (Div. I-III)
154453 Function and structure of neuromodulatory inputs to the cerebral cortex 01.01.2015 Sinergia

Abstract

Cortical map plasticity and learning are thought to rely on structural and activity-dependent forms of plasticity. Hebbian-like plasticity, in which neurons that fire together wire together, is thought to be a key process. For example, long-term potentiation (LTP) of synapses may serve to strengthen pre-established synapses and stabilize newly formed synapses between neurons that are co-activated. The relationship between coincident neuronal activity, cortical plasticity and structural network changes in vivo remains unclear, and is the subject of the current proposal.We hypothesize that (exogenously) forced coincident activity of neurons in the mouse somatosensory cortex in vivo will evoke structural synaptic changes and consequently drive alterations in their receptive fields. In our research proposal we aim at finding causal relationships between synaptic structure dynamics and receptive field plasticity in the barrel cortex.We will follow a targeted approach in which we employ three recently developed cortical activity-dependent plasticity paradigms. In the first approach we will use a rhythmic whisker stimulation protocol (a purely sensory stimulus) to elicit LTP in layer 2/3 (L2/3) pyramidal cells. In the second approach we will utilize the light-gated channel channelrhodopsin-2 (ChR2) to non-invasively elicit LTP, by combining whisker-evoked synaptic input with photostimulation-mediated activation of various cortical neuronal networks. In the third approach we will investigate the structural consequences of a photostimulation-based learning task. In all approaches, we will perform 2-photon laser scanning microscopy of fluorescent proteins (XFPs) that mark synaptic morphology (cytosolic XFPs, PSD-95-XFP, Synaptophysin-XFP) and/or genetically encoded Ca2+ sensors (GCaMPs) to monitor over days to weeks synaptic structural dynamics and the size and strength of receptive fields respectively. Since plasticity will be specifically induced in a small subset of neurons and be confined to anatomically well-defined networks we will be able to compare the plasticity between those neurons that were activated and those that were not within the same cortical structure. This will allow us to make strong predictions about the causality between the various forms of plasticity. Our proposal will further our understanding of the links between structural and functional aspects of activity-dependent plasticity. This may help to advance the design of strategies towards the treatment of traumatic brain injuries or neurodegenerative and psychiatric diseases that are characterized by synaptopathies.
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