Pasteur Institute
Department of Neuroscience
Unité Imagerie Dynamique du Neurone
25, rue du Dr Roux
75724 Cedex 15 - Paris
France

+33 1 45 68 80 54
+33 1 44 38 91 58
david.digregorio@pasteur.fr

Job opportunities

Probing synaptic function with light

Understanding brain function requires an understanding of the communication between groups of neurons via synapses. Moreover, synaptic function is known to be altered in certain diseases and is often the site of action of clinically useful drugs. In our laboratory we study the cellular properties and molecules underlying the strength, time course, and plasticity of synaptic signaling –all parameters thought to underlie such brain functions as memory storage. To date much of our knowledge of synaptic behavior arises from electrophysiological methods such as patch-clamp. However the spatial and temporal limitations of these tools preclude a more in-depth understanding of synaptic function at single synaptic contacts. To overcome these limitations we have supplemented these classical methods with optical techniques which allow us to use light to monitor and manipulate neuronal function within brain tissue. Projects include the use of simultaneous electrophysiology and state-of-the-art single and multi-photon confocal microscopy.  We also take advantage of molecular tools such as transgenic mice expressing genetically encoded fluorescent probes to visualize neurons and their synaptic contacts. We expect that the experimental findings will provide important insights into the behaviour of synapses and how they contribute to neuronal communication within a network.

Bradley, J., Luo, R., Otis, T.S. and DiGregorio, D.A., Submillisecond optical reporting of membrane potential in situ using a neuronal tracer dye. J. of Neuroscience (2009, in press).

Lutz, C, Otis, T, DeSars, V., Charpak S., DiGregorio, D. A., and Emiliani, V. Holographic photolysis of caged neurotransmitters. Nature Methods, 5(9):821-827 (2008).

DiGregorio, D.A., Rothman, J., Nielsen, T., and Silver, R.A. Desensitization Properties of AMPA Receptors at the Cerebellar Mossy Fiber–Granule Cell Synapse Journal of Neuroscience, 27(31):8344–8357 (2007).

Nielsen, T.A., DiGregorio, D.A. and Silver, R.A(2004):Modulation of glutamate mobility reveals the mechanism underlying slow-rising AMPAR EPSCs and the diffusion coeffi cient in the synaptic cleft. Neuron:757-771.

DiGregorio, D., Nusser, Z., & Silver, R.A(2002):Spillover of glutamate onto synaptic AMPA receptors enhances fast transmission at a cerebellar synapse. Neuron:521-533.

DiGregorio, D.A., Peskoff, A., and Vergara, J.L.(1999):Measurement of action potential-induced presynaptic calcium domains at a cultured neuromuscular junction.7846-7859.

Brain slice electrophysiology

Calcium imaging

Voltage dye imaging

Confocal microcosopy

FRAP