2021 Post-doctoral Non-clinical Fellowship
Investigating cerebellar-thalamic-prefrontal circuits in a model of autism spectrum disorder
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by persistent deficits in communication, social interaction and accompanied by restricted, repetitive patterns of behaviour. ASD affects approximately 700,000 individuals in the UK, yet relatively little is understood about its underlying pathophysiology. ASD is often categorized as a network disorder driven by an imbalance between excitatory and inhibitory components. Many symptoms in ASD are linked to networks that include the cerebellum and prefrontal cortex (PFC), with the brains of ASD patients displaying pathologies in both regions. Despite being anatomically located at the opposite ends of the brain, these structures are linked via connections through a mid-brain structure called the thalamus. In this project, I will use an established pre-clinical model of ASD to study the changes in the excitation/ inhibition balance in the neural circuit that connects the cerebellum to PFC. Using a combination of cutting-edge techniques including anatomical tracing and electrophysiology combined with optogenetics, I aim to identify the specific cell types that show altered activity in this circuit, testing hypotheses that propose a key role for the cerebellum in ASD. Further, using chemogenetic tools, I aim to mechanistically link these cellular and circuit-level deficits to ASD-like behaviours. Overall, this study aims to first identify and then reverse the underlying locus of circuit failure in this model of ASD, in the hope that this may offer novel therapeutic insights.