Meeting Abstract
97.6 Monday, Jan. 6 14:45 Cannabinoid Receptor-Mediated Changes of Mitral Cell Activity through Modification of Synaptic Input in the Main Olfactory Bulb HEINBOCKEL, T.*; WANG, Z.-J.; SUN, L.; Howard University, Washington, DC; Howard University, Washington, DC; Howard University, Washington, DC theinbockel@howard.edu
Marijuana (cannabis) is the most commonly abused illicit drug in the USA. Its bioactive ingredient, Δ9-tetrahydrocannabinol, THC, activates cannabinoid receptors (CB1R) in the brain in the same manner as brain-produced endogenous cannabinoids (endocannabinoids, eCBs). The eCB system has emerged as an important neuromodulatory system during normal brain function and involves CB1R and eCBs. Neurons in the main olfactory bulb (MOB) express high levels of CB1R. Our understanding of the functional role of CB1R for olfactory processing is in its infancy. In mouse brain slices, we used whole-cell patch-clamp recordings to study how CB1R regulates the activity of mitral cells (MCs), key MOB output neurons. Our data shows that eCBs mediate strong effects in MCs. We hypothesize that eCBs are modulators of feedforward inhibition of MCs. CB1R agonists evoke membrane depolarization, increased action potential firing, and an inward current in MCs, while CB1R antagonists reduce firing and evoke an outward current. CB1R actions on MCs are eliminated in slices in which the olfactory nerve layer and glomerular layer are microsurgically removed showing that the glomerular layer is the site of CB1R action. Periglomerular cells (PGCs), GABAergic interneurons, show an inverse response pattern to CB1R activation compared to MCs, suggesting that CB1R indirectly regulates MC activity as a result of PGC activation. This hypothesis is supported by our data showing that cannabinoids modulate synaptic transmission from PGCs to MCs. We propose that CB1R directly regulates PGC activity to control GABA release and, in turn, regulates MC activity. Support: Whitehall Foundation, U.S.-PHS grants GM08016, MD007597.
