Mental retardation (MR) is a major cause of children handicap in developed countries. It concerns about 1 to 3% of the general population. 25 to 50% of the severe cases (IQ<50) are due to genetic mutations. Most of monogenetic MR originate in mutations of X genes some coding for synaptic proteins. In most XLMR gene mutations, no major alterations of SNC morphology and structure are found both in humans and in corresponding mouse models, suggesting that only subtle modifications of neuronal and/or synaptic functions are present in MR brains. Therefore, we can anticipate that only a part of the neuronal “repertoire” is perturbed, which nevertheless leads to important functional consequences.

Our aim is to explore as widely as possible both neuronal and synaptic functions. We choose an in vitro approach based on acute slices of mouse brain taken from wild-type or mutant mice. Physiology is examined using electrophysiology (patch clamp, whole cell and cell-attached modes) and dynamic fluorescent cell-imaging (2P excitation Figure 2).