Grant: Project Grant

Electroconvulsive therapy (ECT) is widely used as a therapy for mental illness, and is the most effective treatment for patients who suffer from drug-resistant depression. Unfortunately, many patients avoid ECT treatment due to its side effects on memory. Generally, patients reports difficulties remembering information learned around the time of treatment, but the duration of the impairment and the exact types of memory that are impaired remains unclear. Minimizing these side effects not only requires identification of the types of memory that are affected, but also depends upon an understanding of how ECT affects brain circuits involved in memory. This is very difficult to examine in human patients, but can be probed using animal models of electroconvulsive shock (ECS). The current proposal will therefore use a mouse model of ECS to characterize how ECS affects memory and relevant neural circuits. One major consequence of ECS is the increased birth of newborn neurons (neurogenesis) in the hippocampus, a brain region centrally involved in memory. We propose that the addition of large amounts of new neurons disrupts hippocampal circuits, which causes amnesia shortly after ECS. Here we will examine how ECS alters the properties of new neurons, and we will test whether inhibition of neurogenesis spares memory in the face of ECS. Collectively, this project will generate important knowledge regarding the effects of ECS on cognition, which is needed to ultimately minimize side effects and improve treatment rates and outcomes for human ECT patients.