PhD student in two-photon microscopy in the cerebellum (M/F)

The Cellular and Integrative Neuroscience Institute (INCI) is a CNRS research laboratory in partnership with the University of Strasbourg, comprising 9 teams (130 people), whose mission is to explore the nervous system and its pathologies. The candidate will be supervised by Philippe Isope and researchers from the Neuronal Network Physiology team.

The main aim of this thesis project is to study the functional consequences of dominant gain-of-function (GoF) mutations in the CACNA1G gene causing a severe neurodevelopmental disorder characterized by cerebellar atrophy in childhood (ChCA, also known as SCA42ND). CACNA1G encodes Cav3.1, a voltage-gated T-type calcium channel widely expressed in the nervous system, particularly in the cerebellum, cortex and thalamus. Cav3.1 is involved in electrical and calcium signaling in neurons, including synaptic depolarization, in connection with its dendritic localization.
We will study this mutation using a newly developed mouse model in which one of the mutations identified in humans has been introduced and is expressed under the control of CRE recombinase. In this way, we can express the mutation specifically in Purkinje cells of the cerebellum. Our preliminary data show that, under these conditions, the animals display disorders similar to those observed in humans. We will study how calcium signaling is affected in Purkinje cells and what the physiological consequences are. Experiments will be carried out in vitro on mouse cerebellum slices, or in vivo by combining electrophysiological recordings with calcium imaging using a biphoton microscope. In this way, we will be able to observe the consequences of this gain-of-function mutation on calcium signaling in Purkinje cell dendrites, as well as on the functioning of cerebellar networks in awake animals.