Multiple and opposing roles of cholinergic transmission in the main olfactory bulb

The main olfactory bulb is a critical relay step between the olfactory epit helium and the olfactory cortex. A marked feature of the bulb is its massiv e innervation by cholinergic inputs from the basal forebrain. In this study , we addressed the functional interaction between cholinergic inputs and in trinsic bulbar circuitry. Determining the roles of acetylcholine (ACh) requ ires the characterization of cholinergic effects on both neural excitabilit y and synaptic transmission. For this purpose, we used electrophysiological techniques to localize and characterize the diverse roles of ACh in mouse olfactory bulb slices. We found that cholinergic inputs have a surprising n umber of target receptor populations that are expressed on three different neuronal types in the bulb. Specifically, nicotinic acetylcholine receptors excite both the output neurons of the bulb, i.e., the mitral cells, as wel l as interneurons located in the periglomerular regions. These nicotine-ind uced responses in interneurons are short lasting, whereas responses in mitr al cells are long lasting. In contrast, muscarinic receptors have an inhibi tory effect on the firing rate of interneurons from a deeper layer, granule cells, while at the same time they increase the degree of activity-indepen dent transmitter release from these cells onto mitral cells. Cholinergic signaling thus was found to have multiple and opposing roles in the olfactory bulb. These dual cholinergic effects on mitral cells and int erneurons may be important in modulating olfactory bulb output to central s tructures required for driven behaviors and may be relevant to understandin g mechanisms underlying the perturbations of cholinergic inputs to cortex t hat occur in Alzheimer's disease.