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Analysis of Cortical Circuits Related to ASD Gene Candidates

Cold Spring Harbor
State/Province Full: 
New York
United States

Although autism is among the most heritable of the common neuropsychiatric disorders, it is increasingly clear that no single gene mutation is responsible for all or even most cases. A growing number of genes have been implicated in the etiology of autism, but the candidate genes form a very heterogeneous collection. What do these genes have in common? What is the “final common pathway” that leads to autism? We hypothesize that this heterogeneous collection of autism gene candidates leads to dysfunction at the level of neural circuitry that is more homogeneous and thus easier to understand. This project aims to develop an efficient way of studying, in rodents, the deficits in neural circuitry resulting from the perturbation of autism candidate genes. The investigators will disrupt the function of candidate autism genes and use a combination of in vitro and in vivo technologies to probe for circuit level effects. They will use this strategy to test a leading hypothesis about the circuit dysfunction underlying autism, namely that autism results in a functional imbalance between excitatory and inhibitory synaptic activity. Rat auditory cortex will be used as a model system. Sensory abnormalities, particularly in the auditory domain, are one of the characteristic signs of autism. The initial focus will be on the neuroligins, a candidate gene family implicated in autism. In summary, this project proposes to develop a general and efficient strategy for relating genetic and physiological dysfunction in rodent models of autism. What this means for people with autism: Although the causes of autism may be many, understanding the circuit effects of autism genes will lead to a better understanding of how treatments can be designed to target the common biological mechanisms underlying autism.