We are using integrated approaches to study the role of the nicotinic receptor. These are human iPS cells, their in vitro and in vivo analysis, two-photon imaging in live animals, and comprehensive behavioural analysis in transgenic rat models.

Over the last years, we have based most of our work on robust Genome-wide Association Studies (GWAS) linking human polymorphisms in genes coding for the nicotinic acetylcholine receptor (nAChR) to smoking. We have focused on a coding Single Nucleotide Polymorphism (SNP) in the CHRNA5 gene, coding for the alpha5 nAChR subunit, and dissected its role in reinforcement, consumption levels, and relapse. These findings have led to an approach of “precision medicine”.

A second pathology addressed is schizophrenia. There also, large-scale GWAS identified the same human polymorphisms. Using advanced two-photon imaging in the wake behaving mouse, we were able to identify a network of cortical interneurons expressing nAChRs, and a key role for the alpha5 SNP in reduced cortical activity reminiscent of “hypofrontality” in human patients. This altered activity is restored by the application of chronic nicotine, lending support to the “self-medication” hypothesis, i.e. psychiatric patients smoke to alleviate symptoms of the disease.

Address :
25-28 Rue du Dr Roux, 75015, Paris

Team leader :
Uwe Maskos
Name of co-team leader :

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Key words : récepteur nicotinique, cellules iPS, imagerie deux-photons, Alzheimer, schizophrénie nicotinic receptor, human iPS cells, two-photon imaging, Alzheimer, schizophrenia