PROJECT: JTC2017: MAGNOLIA

The understanding of neuronal circuits, synaptic mechanisms and modulatory systems involved in the pathophysiology of autism spectrum disorders (ASD) is needed to identify novel therapeutic targets for their treatment. The present project focuses on investigating amygdala function in two well established mouse models of ASD since accumulating evidence suggests that amygdala dysfunctions may be linked to impairments of emotional responses, social behavior, affective states and pain perception, all symptoms linked to ASDs. Our goal is to decipher the amygdala neuronal network and synaptic components involved in the regulation of the behavioral symptoms of ASD. In particular, we aim at investigating their control by the neuromodulatory system associated with metabotropic glutamate receptor 4 (mGlu4), which we recently identified as a putative target in ASD. To that aim, four research teams with complimentary skills will collaborate to address this question using behavioral and electrophysiological approaches, supported by optogenetics and photopharmacology, an innovative promising approach using light-controled drugs to decipher the mechanisms of regulation of brain circuits. We expect that our project will outline novel circuit components impaired in ASD, strengthen the hypothesis that mGlu4 is a therapeutic target for treatment of ASD, and eventually lead to the development of new classes of drugs.