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Mathieu Letellier"Dissecting the specificity of activity-dependent changes in cultured hippocampal neurons"

Abstract :


The human brain contains an estimated 100 billion neurons making together 100 trillions synapses.
Understanding how single synapses form at specific locations, develop and work with the others to fine-tune neural circuitry and the flow of information across the brain remains an enduring challenge for modern biology. If each synapse can be individually tuned, a very large number of memories could, in principle, be stored in the brain. Therefore, the importance of accurately evaluating the specificity of synaptic connectivity and plasticity is evident.
How do neurons decide the location and the weight of each of the hundreds of synapses they form and maintain with their partners? How do neurons manage to produce long-term synaptic changes while maintaining the global homeostasis of the networks they form (i.e., activity within physiological ranges)? Using sparse cultured hippocampal networks, we combine multiple patch-clamp recordings and imaging techniques to describe the distribution of pre- and postsynaptic strengths in a network where distinct inputs are identified and controlled. This approach allows us to study how long-term plasticity at one particular input modifies the distribution of synaptic strengths on a post-synaptic neuron. Our results indicate pre- and post-synaptic changes at stimulated synapses but also at non-stimulated synapses suggesting the existence of some heterosynaptic crosstalk. We discuss the possibility that such heterosynaptic crosstalk allows the coexistence of long-term synaptic changes and synaptic homeostasis on a same neuron.

Selected publications

Vitureira N, Letellier M, White I, Goda Y (2011). Differential control of presynaptic organization and neurotransmitter release by postsynaptic N-cadherin and β-catenin. Nature Neuroscience Dec 4. [Epub ahead of print].

Vitureira N*, Letellier M*, Goda Y (2011). Homeostatic synaptic plasticity: from single synapses to neural circuits. Curr Opin Neurobiol Oct 7. [Epub ahead of print].

Letellier M, Wehrle R, Mariani J*, Lohof AM* (2009) Synapse elimination in olivo-cerebellar explants occurs during a critical period and leaves an indelible trace in Purkinje cells. Proc Natl Acad Sci USA (direct submission) 106(33):14102-7.

Olivier Thoumine