Understanding the role of the frontal cortex during cognitive flexibility in Fmr1 knock outs

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PROJECT SUMMARY Autism spectrum disorder (ASD) is a neurodevelopmental disorder where individuals exhibit deficits in cognitive flexibility. Purpose: This proposal will record from the frontal cortex of Fmr1 KOs (model of Fragile X syndrome) during cognitive flexibility tasks and assess how neural hyperexcitability within the KOs impacts reversal learning and shifts of attention. Methods: Fmr1 KOs and wildtype rats will be trained on categorical perception tasks with touchscreens in operant chambers. Single-unit neurophysiology and local field potentials will be collected from the frontal cortex (including the anterior cingulate) during the tasks. It is important to understand how altered neural function within the KOs impacts cognitive function and learning. This project will compare neural activity from putative pyramidal and interneurons to examine differential functions during cognition. Examining these differences in neural function between KOs and WT will enhance our understanding of how cortical excitability impacts cognition. The local field potentials can provide templates of neural signatures that in future studies can be compared to electroencephalography data from humans with ASD or Fragile X.