Daniel J. Spergel, PhD

Dr. Spergel’s diabetes-related research will focus on calcium (Ca²⁺) signaling and projections of glucose-excited (GE) neurons in the ventromedial nucleus (VMN) of the hypothalamus. These neurons, known to be important for increasing blood glucose concentration in response to hypoglycemia (when they are inhibited) by increasing glucagon secretion through the autonomic nervous system, may also help regulate meal initiation and termination. That would make them, along with other populations of GE neurons in the arcuate nucleus and lateral hypothalamus, an excellent target for treating obesity and type 2 diabetes (in which they may exhibit altered glucose sensitivity or responsiveness). In GE neurons, physiologic elevations in extracellular glucose concentration ([glucose]_o) depolarize the plasma membrane, by raising the cytosolic ATP:ADP ratio and closing K_ATP channels (as in pancreatic ß-cells) in addition to other mechanisms, resulting in increased firing rate, Ca²⁺ channel activation, and increased cytosolic Ca²⁺ concentration ([Ca²⁺]_i), which is required for them to release neurotransmitters that affect blood glucose levels and possibly food intake. Dr. Spergel’s lab will use electrophysiological, imaging, and immunohistochemical approaches to determine which voltage-gated Ca²⁺ channel (VGCC) subtypes and Ca²⁺ mobilization pathways mediate changes in [Ca²⁺]_i in GE neurons in the VMN in mouse brain slices in response to changes in [glucose]_o and other metabolic signals, and to map the dendritic and axonal projections of these GE neurons to identify the brain regions where they synapse with other neurons.