Meeting Abstract

55.5  Thursday, Jan. 5  Cannabinoid Receptor-Mediated Regulation of Neuronal Activity and Signaling in Glomeruli of the Main Olfactory Bulb HEINBOCKEL, T.*; WANG, Z.-J.; SUN, L.; Howard Univ. Coll. of Medicine, Washington, DC; Howard Univ. Coll. of Medicine, Washington, DC; Howard Univ. Coll. of Medicine, Washington, DC

Glomeruli in the main olfactory bulb (MOB) are the initial sites of synaptic processing and contain at least three types of neurons collectively referred to as juxtaglomerular (JG) cells. JG cells include periglomerular (PG) cells, external tufted (ET) cells, and short axon (SA) cells. In glomeruli, PG cells form inhibitory GABAergic dendrodendritic synapses with ET cells. ET cells form excitatory glutamatergic dendrodendritic synapses with PG and SA cells. Neurons in the MOB express cannabinoid receptors, CB1R. The function of CB1R and their endogenous activators, endocannabinoids, for neuronal signaling in glomeruli is unknown. In mouse brain slices, we used whole-cell patch-clamp recordings to study the role of CB1R in regulating the activity and signaling of PG and ET cells. A CB1R antagonist evoked membrane depolarization and increased action potential firing in PG cells, while CB1R agonists inhibited PG cells. Blockers of synaptic transmission (ionotropic glutamate and GABA-A receptor antagonists) failed to block CB1R-evoked modulation of PG cell activity, suggesting that cannabinoids had direct effects on PG cells. In the presence but not in the absence of synaptic blockers, ET cells showed a response to CB1R activation similar to PG cells. A CB1R antagonist modestly activated ET cells and an agonist inhibited ET cells. A pulse of depolarizing current injected into an ET cell or a train of depolarizing pulses evoked suppression of IPSCs suggesting retrograde endocannabinoid signaling in the MOB, namely, depolarization-induced suppression of inhibition (DSI) in ET cells. We hypothesize that sustained burst firing of ET cells triggers the release of endocannabinoids which in turn directly control PG cell excitability and reduce GABA release from PG cells. This can result in a transient reduction of PG cell inhibitory input to other neurons such as olfactory nerve, mitral cells and ET cells. Support: Whitehall Foundation, U.S. PHS grants S06GM08016 (MBRS-SCORE, NIGMS/NIH), U54NS039407 (SNRP, NINDS/NIH), 2G12RR003048 (RCMI, NIH-NCRR).