Glucose Sensitivity of Mitral Cell Neurons of the Olfactory Bulb

DESCRIPTION (provided by applicant): The ability to find and ascess the quality of palatable food is dependent on external sensory stimuli, such as olfactory and visual cues. The need to find food is signalled to the brain by changes in feeding-related hormones and metabolites such as insulin, leptin and glucose. Blood and brain levels of glucose and insulin fall and rise acutely with feeding state and are chronically elevated during obesity and diabetes. Fasted animals perform better in olfactory tests. Acute insulin application has been found to suppress the current of a voltage-gated potassium channel (Kv1.3) prominently expressed in mitral cells of the olfactory bulb as well as modulate the spontaneous activity of the mitral cell. Together these results suggest that the mitral cell is able to sense feeding state by feeding-related hormones and metabolites at the level of the olfactory bulb. This proposal will address the following questions: 1. Is mitral cell electrical activity acutely modulated by changes in glucose and are potassium channels, including Kv1.3, involved? 2. How do chronic glucose and insulin modulate mitral cell electrical activity? To answer these questions various concentrations of metabolically active and inactive isoforms of glucose will be acutely applied during whole-cell current- and voltage-clamp olfactory bulb slice mitral cell recordings, and chronically applied for 7 days by intranasal delivery of insulin and glucose followed by similar olfactory bulb slice electrophysiological recordings. PUBLIC HEALTH RELEVANCE: The far reaching relevance of this research is in increasing our understanding of how neuronal activity is changed in response to acute feeding-related glucose changes, as well as, in disease states such as hypoglycemia, diabetes and obesity, when glucose levels are chronically depleted or elevated. With the ever increasing obese population in the United States, it will be important to understand how the chemistry of the obese state affects brain function.