Internally Driven: Using Novel Calcium Channelopathies to Assess the Cerebellar Contribution to Motor and Cognitive Impairment

Event Details

Type

RiSI Distinguished Lecture Series

Speaker(s)

Heather Snell, Ph.D., assistant professor, Yale School of Medicine, Yale University

Speaker bio(s)

Throughout my career, I have been very “internally driven” with a goal of investigating rare disorders caused by mutations in ion channels, or channelopathies. Cerebellar Purkinje cells are also “internally driven”, firing with intrinsic pacemaking activity that helps us maintain our motor coordination. The cerebellum, a brain region widely appreciated for controlling motor coordination, is also a hub for the control of attention, emotional regulation and social interaction. The CACNA1A gene is highly expressed in cerebellar Purkinje cells, where it is integral in maintaining the intrinsic pacemaking activity. This gene encodes for the P/Q type voltage gated calcium channels (Cav2.1), and mutations lead to the movement disorder Episodic Ataxia type 2 (EA2). A subset of EA2 patients also display cognitive impairments, with ASD reported in about 25% of patients with CACNA1A mutations. Interestingly, ~ 88% of people with ASD have some form of motor impairment. Cav2.1 channelopathies that lead to both motor and cognitive impairments are appealing candidates to serve as a molecular handle to examine neurodevelopmental disorders. In this seminar, we will discuss the mechanism underlying the trigger induced motor impairment in EA2 that centers around the modulation of the intrinsic Purkinje cell activity, then we use a novel CACNA1A mutations to investigate the cerebellar contribution to ASD.

Open to

Tri-Institutional