In the current project, Paul Dudchenko provides a detailed neural and behavioral characterization of three rat models of autism spectrum disorder/intellectual disability (ASD/ID): Fmr1^-/y, Grin2b^+/- and Syngap1^+/-. One of the challenges of developing useful animal models of ASD/ID is linking specific genetic alterations with clear changes in neural function and complex behavior. The current project will address this challenge by examining brain regions in which the Fmr1, Grin2b and Syngap1 genes are expressed and which contain head direction cells — neurons which fire when the animal faces a specific direction and which predict spatial behavior.

The three specific aims are:

(1) to characterize the development of the head direction system in juvenile (P21-24) and adult Fmr1^-/y, Grin2b^+/- and Syngap1^+/- rats (and compare these to control, wild type, littermates).

(2) to assess the long-term stability of neural representations in the retrosplenial cortex. Using endoscope imaging of large numbers of neurons simultaneously, the hypothesis that head direction cell representations are less flexible in Fmr1^-/y, Grin2b^+/- and Syngap1^+/- rats compared to their wild type littermates will be assessed.

(3) to provide a complete characterization of the spatial abilities of adult Fmr1^-/y, Grin2b^+/- and Syngap1^+/- rats. Here, tasks will be used that have been shown to require the head direction cell system.

Together, these experiments are expected to provide an in-depth assessment of neural function and complex behavior in Fmr1^-/y, Grin2b^+/- and Syngap1^+/- rats. By contrasting brain areas with rigid and flexible representations of the outside world, the proposed experiments will test how these change in development and how they change with experience.