Linking circuit dynamics and behavior in a rat model of autism

  • Awarded: 2013
  • Award Type: Targeted: Circuit Dynamics
  • Award #: 291584

Significant progress has been made on identifying and characterizing the molecular and genetic changes that contribute to the altered patterns of brain development and connectivity in autism. We do not yet understand how these cellular changes alter brain circuits or how changes in those circuits cause the behavioral manifestations of autism.

Understanding the causal chain from the cellular to the network to the behavior level is likely to be critical for developing treatments that could restore normal neural circuit function in the brains of individuals with autism.

Loren Frank and his team at the University of California, San Francisco, have previously focused on understanding how the hippocampus and related cortical brain regions support memory storage, memory retrieval and memory-guided decision making. Their work has identified specific circuit activity patterns that underlie these functions.

They found that lesions or inactivation of hippocampal and cortical brain circuits causes specific patterns of repetitive behavior, a common hallmark of autism. Autism is also thought to cause cellular abnormalities in these circuits, and Frank and his group hope to leverage their understanding of the normal patterns associated with memory-driven behaviors to examine network dysfunction in rodent models of autism.

The team’s initial efforts will focus on a rat model of fragile X syndrome, a heritable form of autism. Rats lacking FMR1, the gene missing in fragile X syndrome, show many cellular, behavioral and anatomical abnormalities that are similar to those observed in humans affected by the disorder. Using large-scale multi-electrode recordings in the hippocampal and cortical brain areas of this rat model, Frank and his colleagues aim to uncover behavioral phenotypes and underlying circuit-level changes that drive altered behavior in these animals.

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