Host institution: University of Edinburgh, UK

ESR11 – Characterisation of the cerebellum and emotional networks in a transgenic rat model of autism spectrum disorder (ASD)

This project will characterise fear related cerebellar circuit properties using a range of behavioural, anatomical and electrophysiology/manipulation techniques in a rodent model of ASD.

A growing body of literature suggests that many behavioural and pathological changes in ASD can be associated with cerebellar circuit dysfunction. Indeed, multiple rodent models of ASD display cerebellar and behavioural abnormalities characteristic of impairments identified in individuals with autism, including fear and anxiety. Furthermore, unpublished work from our group has revealed robust fear phenotypes in transgenic rat models of ASD.

Given that prediction errors, encoded in cerebellar circuits, are thought to be essential to the fear extinction process and likely underlie many core ASD phenotypes, such deficits may thus reflect aberrant connectivity/activity within distributed cerebellar-fear circuits.

Therefore, this project will map fear related circuit cerebellar circuit activations (e.g. via cFOS) in a transgenic rat model of ASD coupled with in vitro/vivo electrophysiology to record interactions between specific cerebellar regions and emotion networks across a fear conditioning paradigm. Finally, manipulation of specific cerebellar output pathways may be used in an attempt to rescue fear behavioural deficits. The results will be compared and contrasted with those obtained in ESRs 1, 6 and 7. Collaboration with Paris on circuit manipulation experiments.

These experiments will determine how distributed cerebellar-fear circuits contribute to emotional processing in a rat model of ASD.

Planned secondments: AtaxiaUK, month 13, purpose: training in NGO work; Paris, month 19-20, purpose: training in viral/optogenetic tools.