SynAMPAdhesionProject reference: 334218
Funded under :
Synaptic functions of integrin-mediated cell adhesion in physiological conditions and autism-related abnormalities in mice
Total cost:EUR 100 000
EU contribution:EUR 100 000
Call for proposal:FP7-PEOPLE-2012-CIGSee other projects for this call
Funding scheme:MC-CIG - Support for training and career development of researcher (CIG)
Brain function critically depends on how neurons communicate with each others at specialized contact sites, the synapses. Cell adhesion molecules (CAMs) are key synaptic proteins that provide the molecular framework for organizing structural and functional aspects of synaptic connections. However, little is known about the underlying molecular mechanisms. We do not know how CAMs dynamically regulate synaptic strength in response to trans-synaptic interactions and how alterations in the function of some CAMs lead to neurodevelopmental disorders.
We will investigate how the CAMs integrins, present on the postsynaptic side of excitatory synapses, control synaptic efficacy by regulating the properties of glutamate receptors in response to extracellular ligand binding, and how autism-related abnormalities in mice arise from dysfunctions in synaptic integrins. To this end, we will use a multidisciplinary approach to investigate brain function at the molecular, synaptic and behavioral level: we will employ STORM microscopy to examine the physiological relevance of integrin interactions for the submicroscopic organization of synapses, we will use integrin KO mice and viral injections to manipulate expression and activity of integrins in specific neurons, we will investigate synaptic function by electrophysiology in ex vivo brain slices and we will perform behavioral studies in live animals. Findings at all levels will be tightly correlated to understand how alterations in the nonlinear relationship between molecules, synapses and networks translate into behavioral impairments.
The applicant has an internationally recognized broad expertise in synaptic physiology and cell adhesion, acquired while at UCL (UK) in the laboratory of Dr. Goda, who has now relocated her research group to RIKEN (Japan). A successful integration of the applicant in IIT (Italy) will contribute to retain in Europe unique scientific knowledge and create lasting scientific collaborative networks.
EU contribution: EUR 100 000
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