Follow-On: The cortical head direction system as a model for systems-level alterations in three rat models of Autism Spectrum Disorder/Intellectual Disability

This 6 month project is an extension to the original project to assess the neurophysiology and behaviour of rodent models of neurodevelopmental disorders:

A significant challenge in characterisation of animal models of neurodevelopmental disorders is identifying links between specific genetic alterations and complex behaviors (Crawley, 2012). The problem is three-fold: first, genes of interest are often widely expressed in the forebrain, making it difficult to dissociate between direct and indirect effects on local circuit-level function. Second, circuit-behavior linkages are themselves often not well understood. Third, compensation mechanisms that emerge throughout development can occlude the primary circuit dysfunctions. Together, these issues present formidable obstacles, as identifying tractable gene-circuit-behavior pathways is a prerequisite for designing interventions. To address this problem, our consortium will exploit one of the most robust cognitive circuits in the rodent brain, the head-direction (HD) system, to compare three rat models of Autism Spectrum Disorder (ASD)/Intellectual disability (ID): Fmr1-/y , Grin2b+/- and SynGAP1+/- . The comparison will use cutting edge electrophysiological and imaging techniques, coupled with naturalistic behavioral assays, to provide a thorough characterisation of these three gene-circuit behavior pathways. The data generated will provide a clear foundation for subsequent rescue and compensation studies.