Channelopathies

Disorders of brain function such as autism have devastating efects on individuals and families and pose a formidable challenge for neuroscientific understanding. Autism arises from many genes, but a rare form of the disorder (Timothy syndrome, TS) can be generated by alteration of a single nucleotide, switching a single amino acid in the L-type Ca2+ channel. We have clarified the functional effects of this mutation on channel function, and the consequences of increased L-type Ca2+ influx on synaptic integration in brain slices. Ultimately, this 'bottom-up' approach to TS pathogenesis will be joined with studies of other genetic defects associated with autism, in collaboration with other groups, using mice to model the impact of multiple lesions. We are devising new approaches to spotlight single neurons whose genetic properties have been modified in the context of larger network.