Project

Back to overview

Molecular Controls Over the Development and Plasticity of Sensory Topographic Maps in the Neocortex

English title Molecular Controls Over the Development and Plasticity of Sensory Topographic Maps in the Neocortex
Applicant Jabaudon Denis
Number 123447
Funding scheme SNSF Professorships
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 01.08.2009 - 31.07.2013
Approved amount 1'542'583.00
Show all

Keywords (7)

cortical maps; cortical plasticity; thalamocortical connectivity; cortical development; nervous system development; nervous system plasticity; neural repair

Lay Summary (English)

Lead
Lay summary
Molecular Mechanisms of the Development and Plasticity of Topographic Maps in the NeocortexThe current research project aims at identifying the molecular controls over the generation of topographic neuronal maps in the brain during development and their plasticity after injury. In the neocortex, neurons that process peripheral input from the sense organs are located in specialized areas such as the somatosensory cortex and the visual cortex, within which they distribute and connect topographically; in the somatosensory cortex, this topography effectively generates a sensory map of the body on the cortical surface. A similar organization exists in the motor cortex, where neighboring motoneurons control congruous muscles. Currently, little is known about the molecular mechanisms that are responsible for the patterning of these specialized cortical areas during brain development and their plasticity after injury. Here, we address this topic by investigating the molecular programs that control cell-subtype specific differentiation of distinct classes of neurons that form topographic maps, during development and after injury, towards potential paths for nervous system circuit repair.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons
Denis Jabaudon (2013), In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons, in Nature Neuroscience, 16.
Development and plasticity of thalamocortical systems.
Jabaudon Denis, López Bendito Guillermina (2012), Development and plasticity of thalamocortical systems., in The European journal of neuroscience, 35(10), 1522-3.
Patterning of pre-thalamic somatosensory pathways.
Pouchelon Gabrielle, Frangeul Laura, Rijli Filippo M, Jabaudon Denis (2012), Patterning of pre-thalamic somatosensory pathways., in The European journal of neuroscience, 35(10), 1533-9.
Unveiling the diversity of thalamocortical neuron subtypes.
Clascá Francisco, Rubio-Garrido Pablo, Jabaudon Denis (2012), Unveiling the diversity of thalamocortical neuron subtypes., in The European journal of neuroscience, 35(10), 1524-32.
Excess of serotonin affects neocortical pyramidal neuron migration.
Riccio O, Jacobshagen M, Golding B, Vutskits L, Jabaudon D, Hornung J P, Dayer A G (2011), Excess of serotonin affects neocortical pyramidal neuron migration., in Translational psychiatry, 1, 47-47.
ROR{beta} Induces Barrel-like Neuronal Clusters in the Developing Neocortex.
Jabaudon Denis, Shnider Sara, Tischfield David, Galazo Maria, Macklis Jefferey (2011), ROR{beta} Induces Barrel-like Neuronal Clusters in the Developing Neocortex., in Cerebral Cortex, 8282, 1-11.
Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI
Srubek Giulio*, De Leonibus Elvira*, Jabaudon Denis*, Mele A, Macklis JD, Studer M (2009), Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI, in PNAS, 107(8), 3576-3581.
SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development.
Azim Eiman, Jabaudon Denis, Fame Ryann M, Macklis Jeffrey D (2009), SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development., in Nature neuroscience, 12(10), 1238-47.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Swiss Society for Neuroscience Meeting 02.02.2013 Genève
Synaptic Basis of Disease 11.07.2012 Genève
Riken Brain Institute Seminars 04.04.2012 Tokyo, Japan
Universidad Autonoma de Madrid Seminar Series 10.02.2012 Madrid, Spain
International Society for Devlelopmental Neuroscience 11.01.2012 Mumbai, Inde
French Neuroscience Meeting 25.05.2011 Marseille, France
Oxford University Cortex Club 28.04.2011 Oxford University
Swiss Society for Neuroscience Meeting 26.03.2011 Basel
Lemanic Neuroscience Meeting 29.11.2010 Geneva
FENS 03.07.2010 Amsterdam


Self-organised

Title Date Place
Development and Plasticity of Thalamocortical Systems Meeting 31.01.2011 Arolla, Switzerland

Associated projects

Number Title Start Funding scheme
128821 High-resolution ultrasound imaging for micro-targeted in vivo delivery and monitoring of cells, genes, and biomaterials. 01.12.2009 R'EQUIP
146337 Molecular Identity and Development of Layer 4 Thalamorecipient Neurons of the Neocortex 01.08.2013 SNSF Professorships
146337 Molecular Identity and Development of Layer 4 Thalamorecipient Neurons of the Neocortex 01.08.2013 SNSF Professorships

Abstract

This proposal aims at investigating the molecular programs that control the cell-subtype specific differentiation of distinct classes of thalamocortical neurons that form topographic cortical maps, during development, and after injury, towards potential future paths for nervous system circuit repair.In the cerebral cortex, sensory inputs converge to discrete specialized areas such as the somatosensory cortex and the visual cortex via distinct classes of thalamocortical neurons. Within these cortical areas, the topography of the neuronal circuitry reflects the topography of sensory receptors on the body surface; in the somatosensory cortex, neighboring body parts are represented by neighboring neurons, effectively generating a point-to-point map of the sensory periphery within the cortex. Understanding the molecular controls over the development and plasticity of this topographic thalamocortical connectivity is of critical importance since in humans, recovery of function after central nervous system injury, such as after stroke or traumatic brain injury, is largely determined by the extent to which these maps can reorganize. Using the whisker-to-barrel cortex circuitry as a model system, here I propose to investigate the molecular mechanisms that control the topographical precision of thalamocortical projections during development and their plasticity after injury.The whisker barrel cortex is the main cortical sensory area of rodents. This area has a stereotypical topography in which individual whiskers are represented by clusters of neurons called "barrels". Each barrel receives input from a single main whisker via relay neurons located in the thalamus, and adjacent barrels represent adjacent whiskers, generating a precise topographic map of the whisker pad on the cortical surface. Topographic mapping of the whiskers during development is critical for normal sensory information processing, and is severely disorganized by lesions to the afferent whisker pathways during development. The generation of the cortical whisker map during development critically depends on afferent cortical innervation by the axons of thalamocortical neurons located in the medial ventroposterior nucleus (VPM) and posterior medial nucleus (POm) of the thalamus; thalamocortical neurons located in a third thalamic nucleus, the lateral geniculate nucleus (LGN), instead avoid the barrel cortex and direct their axons to a distinct cortical area, the visual cortex. At the time of birth, the axons of VPM neurons invade the prospective barrel cortex in a topographic pattern and reach layer IV where they contact nearby neurons to form the barrels. POm neurons, on the other hand, extend their axons in a pattern that is complementary and mutually exclusive to that of VPM axons, avoiding layer IV barrels to reach targets located mostly in cortical layers I and V. Finally, the axons of LGN neurons reach an entirely distinct cortical area, the visual cortex. The aim of this proposal is to identify critical molecular controls over (1) the distinct cortical target specificity and (2) the plasticity of these distinct classes of thalamocortical neurons. Towards this goal, I propose: (1) to identify and characterize key molecular determinants controlling the generation of prototypical sensory topographic maps. For this purpose, I will compare the stage-specific gene expression of pure populations of VPM, POm, and LGN thalamocortical neurons at critical time points of their development. (2) to identify and characterize key molecular mechanisms controlling the post-lesional plasticity of the whisker barrel cortex during development. For this purpose, I will compare the gene expression of pure populations of input-deprived VPM and POm thalamocortical neurons after unilateral lesion to the whisker sensory pathway with contralateral control VPM and POm thalamocortical neurons. Pure populations of VPM, POm, and LGN neurons will be obtained by retrograde labeling from the whisker barrel cortex and visual cortex followed by fluorescence-activated cell sorting (FACS) of labeled neurons. For (1), gene expression of these closely related populations will be compared using GeneChip microarrays to identify thalamocortical neuron subtype specific genes at three critical stages of development of thalamocortical projections, P1, P3, and P6. For (2), a neonatal unilateral lesion of the infraorbital nerve (which conveys input from the whiskers) will be performed, and a similar strategy will be applied to compare gene expression in control VPM/POm thalamocortical neurons vs. contralateral input-deprived VPM/POm neurons at P6. Functional studies including anatomical labeling, gene expression analysis, and gain/loss- of function approaches will be used to investigate the function of identified candidate genes in barrel cortex patterning and plasticity. Using this approach, I aim to identify critical molecular controls over the development and plasticity of the parallel, interdigitated circuitries formed by the axons of VPM and POm neurons in the barrel cortex and the spatially distinct LGN neuron circuitry. Characterizing these molecular controls is critical not only for understanding how cortical maps are generated, but also, more broadly, to study how neuron circuit specificity is generally programmed in the developing central nervous system.
-