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Office of Autism Research Coordination (OARC) logo

Dissecting the circuitry basis of autistic-like behaviors in mice  

The neurobiology behind the classic signs of autism — repetitive behaviors, impaired social interactions and language deficits — is largely unknown. Based on their studies on mouse models of obsessive compulsive disorder and autism, Guoping Feng and his colleagues at Massachusetts Institute of Technology propose that abnormal signaling between neurons in the cortex and those in the striatum underlies the behaviors associated with autism. Neurons send information to each other via stereotypical paths known as neural circuits to control behavior and body movements, among other processes. For example, many neurons of the cortex signal to neurons of the basal ganglia, which integrate this information into a single output. The neurons of the basal ganglia then signal to the neurons of the thalamus, allowing the action to begin. This neural circuit controls the initiation of most movements, simple to complex. Defects in this circuit have been strongly implicated in autism. Feng and his colleagues plan to pinpoint the neuronal signaling defects in these circuits that lead to repetitive behavior and poor social behavior in mice. In previous studies, the researchers observed these behaviors in mice with a disruption of the PSD95-SAPAP3-SHANK3 scaffolding complex. In neurons of the basal ganglia, this complex anchors the proteins that receive signals from a neuron in the cortex. Using SHANK3-deficient mice to disrupt the scaffolding complex, the researchers plan to disturb neuronal signaling in basal ganglia circuits by combining genetic, optogenetic, electrophysiological and behavioral approaches. Based on these experiments, the researchers hope to learn how abnormal signaling between neurons in the cortex and in the striatum lead to autism-like behaviors. These studies may significantly enhance our understanding of neural circuitry mechanisms of repetitive behavior and impaired social interactions, and help to develop novel strategies for more effective treatment. Project Status
NEW

2010

Funder Simons Foundation
Fiscal Year Funding $175,000.00
Current Award Period 2010-2013
Project Number 178130
Principal Investigator Feng, Guoping
Received ARRA Funding? No
Strategic Plan Question Question 4: Which Treatments And Interventions Will Help? (Treatments)
Subcategory Model Systems/Therapeutic Targets
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 4SB. Standardize and validate at least 20 model systems (e.g., cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012. IACC Recommended Budget: $75,000,000 over 5 years.
Federal or Private? Private
Institution Massachusetts Institute of Technology
State/Country Massachusetts
Web Link 1 Dissecting the circuitry basis of autistic-like behaviors in mice (External web link)
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