Team Leader : Christophe Mulle

Christophe Mulle is a cellular neurobiologist with expertise in cellular electrophysiology of synaptic transmission and plasticity, receptor cell biology, generation of transgenic mice.
Since 1995, he has established a CNRS laboratory in Bordeaux which is interested in the cellular biology and pathophysiology of glutamatergic synaptic transmission and plasticity.

General objective

The research carried out in the group ambitions to link cell biological mechanisms of protein trafficking to synaptic function and dysfunction.
Great efforts are made to implement these questions at an integrated ex vivo or in vivo level in the mouse.

The general long–term objectives of the project aim at answering the following questions:

 What are the molecular mechanisms governing synapse specification and subcellular segregation of glutamate receptors in a given neuron?
 How does synaptic morphology impact on synaptic function at individual synapses, especially during developmental maturation?
 How do presynaptic and postsynaptic parameters integrate to determine proper network function?
 How does synaptic plasticity modify information transfer, network activity and contribute to memory?
 How does synaptic dysfunction cause cognitive disorders, such as mental retardation and Alzheimer’s disease?

Our projects revolve around two main scientific centers of interest: 1) kainate receptors (KARs) and their involvement in brain function and dysfunction and 2) CA3 pyramidal cells which display clearly segregated glutamatergic inputs and are a major stage of hippocampal information processing in learning and memory processes.
The studies rely on a combination of approaches ranging from molecular biology and gene-transfer in the brain to synaptic electrophysiology and live imaging. We have invested considerable effort in the development of gene-transfer methods in slices and in vivo:
(i) biolistic transfection of hippocampal slices for molecular rescue experiments, and
(ii) production of lentiviruses and AAV constructs, and in vivo sterotaxic infection in pups and young mice. These methods are fundamental for a number of projects proposed. Confocal imaging setups coupled to electrophysiology serve to couple electrophysiology to glutamate uncaging, Ca2+ imaging and morphological analysis, and Image acquisition and analysis is made possible thanks to the central imaging facility (BIC).

We are currently developing the use of electrophysiological recordings in vivo (patch-clamp and extracellular recordings), that will be ultimately combined with optogenetic stimulation of neurons.