By taking advantage of our experience in the construction and application of adeno-associated virus (AAV) vectors our preclinical studies (using a mouse toxin model of PD) seek to identify extrasynaptic GABAA receptors as therapeutic targets for treating PD. A major impediment in the field of neuroscience is the availability of pharmacological agents that are selective to individual GABAA receptor subunits. More importantly, systemic administration of these compound do not allow celltype specificity that is crucial to any kind of circuit and behavioral analyses. AAV vectors are superior to other viral delivery vectors because of their sustained transgene expression in non-dividing cells, reduced capsid immunogenicity, and a tropism for neurons. Dr. Kelly Glajch, a postdoc in the lab has prior experience with viral-mediated genetic manipulations and electrophysiological, molecular and behavioral analyses; she is heavily involved in the data collection in this proposal. Our specific aims are: Specific Aim 1: Construction and validation of shRNAs targeting extrasynaptic GABAA receptor; and Specific Aim 2: Behavioral assessment of functional knockdown of extrasynaptic GABAA receptor in the striatum.
|Effective start/end date||1/1/13 → 12/31/13|
- Northwestern Memorial Foundation (Agreement Date: 12/21/12)