The neuron-specific potassium-chloride co-transporter, KCC2, is involved in the regulation of excitatory and inhibitory neuronal activity. It has been identified as a promising therapeutic target for autism. In the current project, Charles Craik’s laboratory and collaborators plan to determine the high-resolution structure of KCC2 with the intention of developing strategies to regulate its activity.

Based on the critical role of silent synapses in developmental neurocircuit refinement, Oliver Schlüter aims to assess whether ASD-risk genes encoding proteins associated with glutamate receptor complexes play a common role in silent synapse development. Using three different ASD mouse models (Shank3, Syngap1 and Nlgn3 deficiency), Schlüter will assess whether alterations in silent synapse maturation represent a common mechanistic defect underlying the distinct phenotypic facets of ASDs.

Sleep plays an important role in cognitive functions such as learning and memory, and sleep disruptions are associated with neurodevelopmental disorders, including Rett syndrome. The current project aims to understand the molecular mechanisms by which sleep supports cognitive function and to test the role of sleep disruption in the progression of Rett syndrome using an MeCP2 knockout mouse model. With detailed knowledge of the mechanisms underlying the restorative functions of sleep, new therapies could be developed to restore sleep in individuals with neurodevelopmental disorders.