How do autism-related mutations affect basal ganglia function?

  • Awarded: 2014
  • Award Type: Pilot
  • Award #: 307866

Significant progress has been made in recent years in identifying genetic factors contributing to autism. Although the genes identified have diverse biological functions, many of them are important for controlling the structure and function of the connection points between brain cells, called synapses. Alterations in synapse function affect the ability of brain cells to communicate with each other, and can lead to imbalanced or inappropriate activity in brain networks.

The majority of basic research in autism has focused on areas of the brain important for higher cognitive functions. However, a core feature of autism is repetitive or restricted behavior, which may arise from dysfunction in a brain region called the basal ganglia. This region controls goal-directed movements and habit learning. Little is known about how mutations in genes associated with autism affect brain cells in the basal ganglia.

Helen Bateup and her colleagues at the University of California, Berkeley propose to address this knowledge gap by using mouse models to investigate the impact of autism-related mutations on synapse function in the basal ganglia. In parallel, they aim to examine whether selectively disrupting autism-related genes in specific cell classes in the basal ganglia is sufficient to induce behavioral changes related to autism.

Bateup and her team will use state-of-the­ art technology to probe the details of how brain cells communicate with each other in a brain region that is likely to be relevant but understudied in autism research. The group will use diverse approaches, ranging from molecular to behavioral analyses, to generate a complete picture of how genetic mutations associated with autism affect brain function at multiple levels. It is their hope that these preclinical studies will identify therapeutic targets and ultimately guide the development of clinical trials for the treatment of autism.

Subscribe to our newsletter and receive SFARI funding announcements and news