Cholinergic modulation of excitability in the rat olfactory bulb: effect of local application of cholinergic agents on evoked field potentials

Abstract

The effect of exogenously applied cholinergic agents upon mitral-granule cell complex activity of the olfactory bulb was studied in anesthetized rats. Output neurons were activated by electrical paired-pulse stimulation (40-80 ms time interval) applied either to the olfactory nerve (orthodromic stimulation) or to the lateral olfactory tract (antidromic stimulation). Evoked field potentials were recorded in the granule cell layer. Cholinergic agents were introduced close to the mitral cell body layer through a push-pull cannula. With both orthodromic and antidromic stimulations, acetylcholine in the presence of eserine (an acetylcholinesterase blocker), did not alter the conditioning volley, while it induced a significant increase in the amplitude of the test volley. This effect could be replicated using the cholinergic agonist carbachol. This attenuation of the paired-pulse inhibition is due to a reduction of the dendrodendritic inhibitory action of granule cells upon relay cells. Muscarinic and nicotinic transmission were studied using antidromic and orthodromic stimulations, respectively. The selective effect of acetylcholine on the test volley was totally abolished by the blockade of the muscarinic transmission (by atropine). The blockade of the GABAergic transmission (by picrotoxin), could also prevent the acetylcholine-induced effect. The results lead us to propose that in deep bulbar layers, acetylcholine may activate muscarinic receptors situated on second-order GABAergic interneurons. These interneurons could in turn inhibit granule cells (first-order interneurons). The nicotinic antagonist d-tubocurarine selectively enhanced the duration of the late component and did not appear to modify early components when stimulation was applied to the olfactory nerve. This effect related to both the conditioning and the test volleys and the enhancement in the duration of depolarization of granule cell dendrites suggests that normal activation of nicotinic receptors contributes to a faster repolarization of granule cells. Since nicotinic receptors belong to the outer glomerular layer, this result points to the existence of interneurons belonging to the periglomerular region where they receive nicotinic input and project to deep layers where they modulate granule cell activity. Taken together, our results suggest the presence of a phasic muscarinic and a tonic nicotinic modulation of bulbar interneuronal activity. Since both could finally reduce the inhibitory action of granule cells, the action of cholinergic afferents would facilitate transmission of bulbar output neurons to central structures.