tVTAforever

The tail of the ventral tegmental area (tVTA), also known as the rostromedial tegmental nucleus (RMTg), is a brain structure discovered 15 years ago that is now considered as the main inhibitory control of midbrain dopaminergic systems. Those systems, mainly arising from the ventral tegmental area (VTA) and the substantia nigra pars compacta, are associated with psychopathologies such as addiction and depression, and with neurological disorders such as Parkinson's disease. The tVTA has initially been described in the rat but a mouse model was still lacking to explore tVTA functions using selective transgenic tools. We now overcame this difficulty. Indeed, we recently identified a developmental transcription factor that is still expressed in adulthood as a selective marker of the GABAergic neurons of the tVTA, and we validated an inducible transgenic mouse line as a perfect model to investigate tVTA physiology. Thus, the tVTAforever project brings together four research groups from three research institutes, with complementary technical expertise, to further investigate tVTA properties and functions. Together we propose to: 1) characterize the connectome, i.e. the synaptic inputs and outputs, of the mouse tVTA; 2) characterize the electrophysiological properties of tVTA neurons in their diversity; and 3) elucidate the role of the tVTA-VTA pathway on the hedonic balance and on natural reward properties. This project will be conducted on female and male transgenic mice, using a combination of viral anterograde and retrograde tract-tracing, in vivo and ex vivo electrophysiological recordings, in vivo calcium imaging in behaving animals through fiber photometry, and chemogenetic and optogenetic manipulations of the tVTA during behavioral tasks. The ambition of this project is to reinforce our knowledge on the tVTA and on the function of the tVTA-VTA pathway to further stimulate research on tVTA neurons functional diversity and on the implications of this diversity in pathophysiologies, addressing here as a first step eating disorders and addiction.