We utilize genetic engineering techniques in mice, in conjunction with electrophysiology, optogenetics, pharmacogenetics and rabies mapping, to elucidate central neurocircuits controlling feeding behavior, body weight homeostasis, and fuel metabolism. Specifically, transgenic, knockout, knockin, and cre-dependent AAV viral approaches (for delivery of optogenetic, DREADD and monosynaptic rabies reagents) are used to manipulate and map neuronal circuits. The goal of these studies is to link neurobiologic processes within defined sets of neurons with specific behaviors and physiologic responses. The ultimate goal is to mechanistically understand the “neurocircuit basis” for regulation of food intake, energy expenditure and glucose homeostasis. Given our expertise in gene knockout and transgenic technology, we can efficiently and rapidly create numerous lines of genetically engineered mice, important examples being neuron-specific ires-Cre knockin mice, which enable cre-dependent AAV technology. This allows us to bring novel, powerful approaches to bear on the neural circuits underlying behavior and metabolism. Our combined use of mouse genetic engineering, brain slice electrophysiology, and whole animal physiology is ideally suited to studying these problems.
Specific areas of interest include:
Neurobiological and neurocircuit basis for leptin action and melanocortin-4 receptor action, role of synaptic transmission and NMDAR-mediated synaptic plasticity within feeding circuits, afferent inputs regulating AgRP and POMC neurons, efferent circuits responsible for effects of AgRP and POMC neurons on feeding behavior, dissection of neural pathways regulating sympathetic outflow and energy expenditure, and finally neural mechanisms by which the brain controls glucose homeostasis.