[855] Les circuits neuronaux dans le néocortex des mammifères

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 (see figure).

a) Diagram of the whisker-to-barrel pathway and chessboard whisker trim-ming.
b) Schematic of a cranial window superposed on a coronal section from a Thy1-EGFP transgenic mouse brain (GFP is black). The intact, exposed dura (gray) is covered with a coverglass (blue).
c) The apical tufts of layer 5 pyramidal neurons can readily be imaged in vivo using 2PLSM.
d) Individual dendritic spines, the sites of synaptic contacts, can be imaged over long periods. Many spines are stable (yellow arrowheads) and some appear and disappear (white arrowhead). Some new spines stabilized (orange arrowheads) after whisker trimming (days 12-28).

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.

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