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Séminaire - Matthew Dalva“Visualizing the dynamics of cell signaling that underlie synapse formation"

Abstract :

Séminaire  du Vendredi , exceptionnellement le lundi 29 en raison  de la "Brain  international conference du 1-2-3   Octobre


The structure of the nervous system varies tremendously across phylogeny; organisms such as the C. elegans function with a few hundred neurons,
whereas humans have tens of billions. Yet communication in all neural circuits is controlled by a remarkably similar, highly specialized site of cell-cell contact known as a synapse. The long-range goal of my research is to discover how synapses are formed and lost, and what impact normal morphology and numbers of synapses have on brain function. Determining how synapses develop and mature will provide insights toward understanding of neuronal networks and brain function.

To determine how synapses are formed and lost, I have focused on understanding the molecules that control their generation. My lab has targeted EphB proteins and their ephrin-B ligands, because we have shown these molecules are required both in vitro and in vivo for normal synapse formation. EphBs are transmembrane signaling molecules and are the largest known family of receptor tyrosine kinases in the mammalian genome that bind to ephrin-Bs, which are transmembrane proteins also capable of signaling. Our findings from the past decade demonstrate that EphBs and ephrin-Bs have a role in: (1) how are specific types of morphological specialization like spines are formed, (2) in dendritic filopodia dependent synaptogenesis, (3) in the control of synapse density; and (4) how are glutamate neurotransmitter receptors directed to the synapse. Recently we have begun to explore the role that EphBs and ephrin-Bs play in the control of migration of cells in the adult brain and developed tools to visualize cell signaling in living neurons.

 

 

Selected publications

Defects in synapse structure and function precede motor neuron degeneration in Drosophila models of FUS-related ALS.
Shahidullah M, Le Marchand SJ, Fei H, Zhang J, Pandey UB, Dalva MB, Pasinelli P, Levitan IB.
J Neurosci. 2013 Dec 11;33(50):19590-8. doi: 10.1523/JNEUROSCI.3396-13.2013.


EphBs: an integral link between synaptic function and synaptopathies.
Sheffler-Collins SI, Dalva MB.
Trends Neurosci. 2012 May;35(5):293-304. doi: 10.1016/j.tins.2012.03.003. Epub 2012 Apr 18. Review.

Scientific focus :

Research and Clinical Interests

The long-range goal of my research program is to understand how synapses and functional neural circuits are generated.

The structure of the nervous system varies tremendously across phylogeny; organisms such as the C. elegans function with a few hundred neurons, whereas humans have tens of billions. Yet communication in all neural circuits is controlled by a remarkably similar, highly specialized site of cell-cell contact known as a synapse. The goal of my research program is to understand how excitatory spine synapses are formed and lost, and what impact the normal morphology and numbers of these structures have on brain function. Because the excitatory synapse is likely to be central to a number of diseases such as addiction, Alzheimer's disease, and autism, our research will have broad impact. more...

Agenda