Nicotinic receptors modulate olfactory bulb external tufted cells via 4 an excitation - dependent inhibitory mechanism

21 Olfactory bulb (OB) glomeruli, the initial sites of synaptic processing of odor information, 22 exhibit high levels of nicotinic acetylcholine receptor (nAChR) expression and receive strong 23 cholinergic input from the basal forebrain. The role of glomerular nAChRs in olfactory 24 processing, however, remains to be elucidated. External tufted (ET) cells are a major source of 25 excitation in the glomerulus, and an important component of olfactory bulb physiology. We have 26 examined the role of nAChRs in modulating ET cell activity using whole-cell electrophysiology in 27 mouse OB slices. We show here that the activation of glomerular nAChRs leads to direct ET cell 28 excitation, as well as an increase in the frequency of spontaneous postsynaptic GABAergic 29 currents (sIPSCs). β2-containing nAChRs, likely the α4β2*-nAChR subtype (* represents the 30 possible presence of other subunits), were significant contributors to these effects. The nAChR31 mediated increase in sIPSC frequency on ET cells was, for the most part, dependent on 32 glutamate receptor activation, thus implicating a role for excitation-dependent inhibition within 33 the glomerulus. β2-containing nAChRs also regulate the frequency of miniature inhibitory 34 postsynaptic currents (mIPSCs) on ET cells, implying nicotinic modulation of dendrodendritic 35 signaling between ET and periglomerular cells. Our data also indicate that nAChR activation 36 does not affect spontaneous or evoked transmission at the olfactory nerve-to-ET cell synapse. 37 The results from this study suggest that ET cells, along with mitral cells, play an important role 38 in the nicotinic modulation of glomerular inhibition. 39