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Synaptic and circuitry mechanisms of repetitive behaviors in autism

Guoping Feng, Ph.D.
Ann M. Graybiel, Ph.D.
Massachusetts Institute of Technology


The neurobiology behind the classic signs of autism — repetitive behaviors, impaired social interactions and language deficits — is largely unknown. Based on their studies on a mouse model of obsessive-compulsive disorder, Guoping Feng and his colleagues at Duke University propose that an imbalance between two circuits of neurons may underlie the repetitive 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. Signals to stop the movement are transmitted from the cerebral cortex to the thalamus via a second, distinct neural circuit.

In a previous study, Feng and colleagues found that disrupting the PSD95-SAPAP-Shank scaffolding complex of signal-receiving proteins in the basal ganglia neurons leads to repetitive behaviors in mice. The work suggested that because the cells cannot talk to each other properly, the neural circuits that control the initiation and cessation of movements are not balanced. The investigators now suggest that the repetitive behaviors associated with autism arise from a similar imbalance between these neuronal circuits.

To test this theory, Feng and colleagues plan to analyze 20 genes known to influence the signaling complex linked to the neural circuitry of repetitive behaviors, searching for mutations that are associated with autism. The researchers also plan to study the relationship between the two circuits by manipulating the activity of basal ganglia neurons in mice. By separately inactivating the neural circuits for movement initiation and cessation, the team hopes to learn how each contributes to motor and behavioral control.


proposalCENTRAL #94602