Aller au contenuAller au menuAller à la recherche

Séminaire impromptu - Frédéric GambinoNonlinear thalamic inputs mediate whisker-evoked heterosynaptic plasticity in the somatosensory cortex

Abstract :

Frédéric Gambino invité par Yann Humeau de l'IINS


Long-term potentiation (LTP) of synaptic connections within layer (L) 2/3 of the somatosensory cortex is thought to underlie sensory experience-dependent cortical map plasticity. One possible mechanism for LTP involves the temporal coincidence of synaptic inputs and somatic action potentials (APs) that back-propagate into dendrites, termed spike-timing dependent (STD) LTP. Indeed, we have previously shown that experience-mediated disinhibition facilitates STD-LTP in L2/3 pyramidal neurons in the barrel cortex. However, spontaneous and sensory-evoked spiking is strikingly sparse in those L2/3 pyramidal neurons. This casts doubt as to whether repetitive and natural whisking would ever produce enough somatic APs to induce LTP. Here we show using in vivo whole-cell recordings and calcium imaging in the anesthetized mice, that repetitive whisker deflections can induce LTP of whisker-mediated synaptic inputs without generating somatic APs. This potentiation was specific to the stimulated whisker, and it required nonlinear NMDARs-dependent plateau depolarization driven by inputs that are relayed in the posterior medial (POm) higher order thalamic nucleus. These inputs are part of the paralemniscal pathway and project in a non-specific manner to the distal dendrites of L2/3 neurons. Together, our data suggest that the activation of paralemniscal somatosensory pathways facilitates the strengthening of spatially segregated synaptic inputs on barrel cortex pyramidal cells.

Selected publications

Spike-timing-dependent potentiation of sensory surround in the somatosensory cortex is facilitated by deprivation-mediated disinhibition.
Gambino F, Holtmaat A.
Neuron. 2012 Aug 9;75(3):490-502. doi: 10.1016/j.neuron.2012.05.020.

Synapses let loose for a change: inhibitory synapse pruning throughout experience-dependent cortical plasticity.
Gambino F, Holtmaat A.
Neuron. 2012 Apr 26;74(2):214-7. doi: 10.1016/j.neuron.2012.04.005.

Scientific focus :

During development, neural circuits in the mammalian neocortex are initially wired up in a stereotypic way, guided by a myriad of intracellular and extracellular molecular cues. Later, connectivity is further sculpted by spontaneous and sensory-evoked activity. Although activity dependent plasticity is most robust during development, it has been shown that neural circuits remain plastic in the adult brain. For example, most sensory representations in the neocortex change in size and/or location upon peripheral lesions and amputations, or even after more subtle changes in experience throughout life. This so called functional plasticity depends on changes in the strength of established synaptic connections, but could also involve structural alterations, including synapse formation and elimination. We are interested in these structural and morphological aspects of synaptic plasticity in the adult brain, and explore the possibility that structural plasticity is involved in long term memory storage, the acquisition of training/experience- based skills, and in functional adaptations of cortical circuits after lesions. With the use of long term in vivo 2-photon laser scanning microscopy (2PLSM) and GFP transgenic mice we have recently shown that novel sensory experience can drive the stabilization of new synaptic connections in the mouse somatosensory cortex.
In the future, we will continue to focus on experience dependent changes in cortical circuits and their synaptic components, as well as on plasticity that is induced by central and peripheral lesions. We will be using in vivo gene transfer techniques, such as transgenic mice, recombinant viral vectors and in utero DNA-electroporation, combined with long term 2PLSM, intrinsic signal optical imaging and local field potential recordings to monitor the dynamics of synaptic proteins, dendrites and axons in relation to the functionality of cortical circuits in the living mouse.

Yan Humeau (bodabour @ gmail.com)