PhD PROPOSAL FOR THE PASTEUR-PARIS UNIVERSITY INTERNATIONAL PROGRAM

 

Deadline for full application: December 15th, 2013

Interviews: March, 2014

Start of the Ph.D.: October 1st, 2014

 

 

Department: Department of Neuroscience

Title of the PhD project: Optical dissection of cerebellar sensory processing in mouse models of Autism

Name of the lab: Unit of Dynamic Neuronal Imaging

Head of the lab: David DiGregorio

PhD advisor: David DiGregorio

Email address: david.digregorio@pasteur.fr

Web site address of the lab:

Doctoral school affiliation and University: ED3C

 

 

 

Presentation of the laboratory and its research topics:

 

My laboratory specializes on the development and application of optical methods for the study information processing in cerebellar and cortical circuits. Biological projects in the laboratory involve electrophysiological recordings in acute slices from wild type and transgenic animals, biophysical analysis, and numerical simulations. Imaging modalities include rapid single and multi-photon imaging intracellular calcium and membrane voltage, as well as photo-uncaging of neurotransmitter.  Optical developments are focused on the improvement of speed and efficiency of multi-photon microscopy as well as the implementation and development of super-resolution imaging methods (e.g. STED microscopy).

 

 

 

Description of the project:

 

Understanding the complexities of information processing within the brain requires more than just knowing the precise neuronal wiring diagram, it also requires a detailed description of the temporal and spatial dynamics of signal flow between and within single neurons connected in a complex network. This daunting task is simplified by studying small groups of connected neurons, or microcircuits. A particularly attractive model microcircuit is that of the cerebellar cortex, because of its ordered, well-defined connectivity and small numbers of different neuron types. Nevertheless, surprisingly little is known about how this microcircuit builds upon its well-known synaptic and cellular properties to dynamically integrate and process sensory information, largely because of the difficulty of measuring dynamic activity of many individual synapses or the ensuing postsynaptic signals in fine dendrites. We use optical methods that improve spatial and temporal limitations of electrophysiological tools to allow the study of single synapse function. The combination of such state-of-the-art methods and transgenic mouse models of neurological disorders can provide insight into the relationship between synaptic proteins and their function on both the cellular, network, and finally behavioral level. Autism spectrum disorders (ASD) affect 1% of children and are diagnosed based on alterations of three behavioral domains: social deficits, impaired language and communication skills, and stereotyped and repetitive behaviors. Many of the genes found to be associated with ASD are highly expressed in the cerebellum. Therefore, in this project we propose to use transgenic mice that are mutated for synaptic genes associated with ASD to characterize the impact of these mutations on cerebellar function using state-of-the-art electrophysiology and imaging techniques. The project proposed here is a collaboration with Pr. Thomas Bourgeron (Institut Pasteur), an expert in the genetics of ASD.

 

 

 

 

References:

 

 

 

 

 

Keywords:

 

Cerebellum, synapse, microcircuits, Autism, mult-photon imaging, calcium, voltage, dendritic integration

 

 

 

Expected profile of the candidate (optional):

 

 

 

Contact:

 

David DiGregorio (david.digregorio@pasteur.fr)

Mis à jour le 16/09/2013