Challenges in social communication are one of the core symptoms of autism spectrum disorder (ASD). The neural circuitry supporting social cognition is broadly distributed across the brain, and the prefrontal cortex and hippocampus in particular are both thought to be crucial nodes in this network. How neural activity in these distributed circuits is coordinated to represent social goals and information, and how this coordinated activity enables social interactions, is still not well understood.

Shantanu Jadhav and his colleagues at Brandeis University have reported key network mechanisms for coordination across hippocampal-prefrontal circuits mediated by multiple neural activity patterns and have linked these patterns to normal cognitive function^1,2. Jadhav hypothesizes a role of this network coordination in social interactions and that changes in network coordination can contribute to altered social interactions in ASD.

In order to test these hypotheses, Jadhav and his team have utilized the unique strengths of the rat as a model system to develop a social cooperation paradigm in paired spatial mazes. They will use this social behavior task to characterize social interactions in Fmr1 knockout rats and other rat autism models in collaboration with the Autism Rat Model Consortium. They will also use high-density in vivo recordings from hippocampal–prefrontal ensembles and closed-loop manipulation techniques to investigate neural coordination mechanisms during social interactions in wild-type and Fmr1 knockout rats.

This work will shed light on network mechanisms underlying long-range coordination in hippocampal–prefrontal circuits for social interactions and address links at the neuronal network level that can bridge genetic characterizations to social behavioral difficulties. The long-term goal of this work will be to develop novel approaches for monitoring and manipulating network coordination, a systems-level target, to address social behavior challenges in ASD.

1. Shin J.D. et al. Neuron 104, 1110-1125 (2019) PubMed
2. Tang W. et al. eLife 10, e66227 (2021) PubMed