University of Edinburgh, UK
Genetic analysis of individuals with autism spectrum disorders (ASDs) and intellectual disabilities (IDs) has led to the hypothesis that monogenic causes of these disorders converge on common cellular pathways. Using rat models of ASDs/IDs, we find that this apparent molecular convergence is not mirrored by convergent pathophysiology of cellular electrophysiology and behaviour. Instead, each model examined demonstrated a unique profile of synaptic and cellular electrophysiological phenotypes and a distinct behavioural ethogram. This gene-specific pathophysiology gives insight into the circuit dysfunction for particular forms of ASD/ID. For example, null mutations in Nlgn3 led to an imbalance in the flight/freeze response to fearful stimuli. This circuit alteration is due to, in part, an increase in the excitability of neurons in the dorsal periaqueductal grey.
Professor Kind is Director of the Simons Initiative for the Developing Brain at the Patrick Wild Centre for Research into Autism, Fragile X Syndrome (FXS) and Intellectual Disability and Professor of Developmental Neuroscience at the University of Edinburgh. He is also Associate Director at the Centre for Brain Development and Repair (CBDR) at the Institute for Stem Cell Biology and Regenerative Medicine (Instem), Bangalore, India. Professor Kind completed his postdoctoral training with Professor Colin Blakemore at Oxford University and Professor Susan Hockfield at Yale University. Professor Kind received his PhD from Oxford University in 1993. He joined the University of Edinburgh in 2020. The Kind laboratory examines the cellular dysfunction associated with monogenic forms of moderate to severe neurodevelopmental disorders. The laboratory focuses on synaptic function, from the physiological and morphological alterations to the behavioural phenotypes associated with mouse and rat models of these disorders. We also test the hypothesis that distinct genetic causes of ID/ASD convergence on common biochemical and cellular pathologies associated that may be amenable to similar therapeutic approaches.