Dissection of Neural Circuit Function and Degeneration from a Subcellular Perspective

Abstract

How do neurons perform the set of signaling functions necessary for proper circuit function? We aim to uncover cellular and molecular mechanisms that shape excitability among different mammalian neurons. We approach these questions in intact brain circuits, using intersectional approaches combining optogenetics, in vivo and ex vivo electrophysiology, 2P imaging, AAV vectors, and transgenic models. Perhaps the most critical neuronal signaling features are action potential firing and synaptic transmission. Neurons regulate these features by spatially segregating different ion channels in the soma, dendrites, and axon. We are now beginning to understand the significance of these cellular processes in terms of circuit function and disease. We are interested in understanding how different cell classes, (e.g., inhibitory neurons) utilize these excitable mechanisms to their advantage in the circuit. Knowledge gained from these studies will fuel the design of robust, cell-type-specific therapeutic approaches against neurological disorders.