Dissecting striatal circuit dynamics during repetitive behaviors in autism

  • Awarded: 2013
  • Award Type: Targeted: Circuit Dynamics
  • Award #: 294295

Learning to automatize actions and form habits is critical for mastering everyday skills and activities such as riding a bike, speaking or writing. However, having overly automatized actions can lead to an overabundance of stereotyped, repetitive behaviors and to lack of control or ability to switch between habits and novel behavioral patterns.

People with autism demonstrate repetitive behaviors and impaired habit learning. Yet the neural circuits underlying these behaviors remain unclear. The dorsolateral striatum is a region of the brain that has been implicated in habit formation and repetitive behavior. Nevertheless, the link between dysfunction of this structure and autism-related repetitive behavior remains elusive. The striatum, the major input structure of the basal ganglia area of the brain, is a complex structure with several sub-circuits, including a ‘direct pathway’ to the output nuclei (striatonigral) and an ‘indirect pathway’ to the output nuclei (striatopallidal), respectively thought to facilitate or inhibit movement.

Rui Costa and his team at the Champalimaud Center for the Unknown in Portugal plan to assess the relationship between repetitive behaviors and habit formation in mice with deletions in the autism-associated genes CNTNAP2 and SHANK3. Costa and his colleagues will be able to image the activity of neurons in the striatum of these mice using a miniature microscope as well as a genetically encoded calcium indicator to visualize neuronal activity during the stereotyped, repetitive grooming and habit formation present in the mice. The researchers aim to directly determine whether manipulating the function of either the direct or the indirect pathway, by activating or inhibiting the activity of these pathways during repetitive behaviors and habit formation, can ameliorate or exacerbate the behavioral symptoms.

Using these methods, Costa and his colleagues hope to identify the striatal neuronal pathway dysfunction mediating repetitive behavior, a core symptom of autism.

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