Cholinergic modulation of neurons in the gustatory region of the nucleus of the solitary tract.

The rostral portion of the nucleus of the solitary tract (rNST) is an obligatory relay for gustatory afferent input on its way to the forebrain. Previous studies have demonstrated excitation of rNTS neurons by glutamate and substance P and inhibition by gamma-aminobutyric acid (GABA) and met-enkephalin (ENK). Despite the existence of cholinergic neurons and putative terminals within the rNTS, there are no data on the effects of acetylcholine (ACh) on rNTS processing. Here, we use patch-clamp recording of rNTS neurons in vitro to examine ACh-mediated responses and voltage-gated conductances in these cells. Results revealed (1) intrinsic voltage-gated inhibition via activation of voltage-gated potassium A-channels (I(A)), found almost exclusively in the medial rNTS, and hyperpolarization-activated potassium/sodium channels (I(h)), found more frequently in the lateral rNST; and (2) ligand-gated inhibition via activation of muscarinic m2 ACh receptors (mAChRs) linked to inward rectifier potassium channels (K(ir)) evenly distributed throughout the rNTS, a mechanism dependent on cholinergic inputs. Muscarinic responses were blocked by AFDX-116, a selective m2 mAChR antagonist, and by BaCl2, an antagonist of K(ir) channels. In addition, many rNTS neurons exhibited excitation via alpha7 and non-alpha7 nicotinic AChRs. Non-alpha7 nAChRs, blocked by 10 microM mecamylamine, occurred more frequently in the lateral rNTS. In contrast, alpha7 nAChRs, blocked by 20 nM methyllcaconitine, were evenly distributed across the nucleus. As previously reported for voltage-activated conductances, none of these currents was related to neuronal morphology. These voltage- and ligand-dependent inhibitory mechanisms would be expected to contribute to the modulation of gustatory processing through the NST.