2015 Seed Grant
Michael Higley, M.D., PhD.
Yale University
The activity of neurons in the brain is determined by the interplay of excitatory and inhibitory synaptic inputs to each cell. Alterations in neuronal inhibition are thought to play key roles in several neuropsychiatric disorders. However, it has been difficult to study the normal function of inhibition in the intact animal, because large-scale changes in inhibitory signaling lead to gross perturbation of brain activity. Here, we use a recently developed approach to disrupt inhibition in only a few neurons of the mouse brain and monitor the activity of these cells using a powerful form of microscopy. Thus, we will investigate how disruption of inhibition leads to changes in cell function without the confounding changes in overall brain activity. These experiments will give us important new insights into how neuronal activity in the healthy brain is generated and how it may be altered in disease.