Heterogeneity of nicotinic acetylcholine receptor expression in the caudal nucleus of the solitary tract

The nucleus of the solitary tract (NTS) is the principal integrating relay in the processing of visceral sensory and gustatory information. In the present study, patch-clamp electrophysiological experiments were conducted using rat horizontal brainstem sections. Pre-synaptic and somatic/dendritic nicotinic acetylcholine receptors (nAChRs) expressed in neurons of the caudal NTS (cNTS) were found to be randomly distributed between pre-synaptic and somatic/dendritic sites (χ2 = 0.72, df = 3, p > 0.87, n = 200). Pre-synaptic nAChRs were detected by their facilitating effects on glutamatergic neurotransmission of a sub-population of cNTS neurons (categorized as “effect-positive”) upon brief picospritzer applications of 0.1–0.5 mM nicotine. These effects were resistant to inhibition by 20 nM methyllycaconitine (MLA) and 4 μM dihydro-β-erythroidine (DHβE), and were replicated by brief picospritzer applications of 0.2–1 mM cytisine. Picospritzer applications of 0.2 mM RJR-2403, a potent agonist of α4β2 nAChRs, did not facilitate synaptic release of glutamate in effect-positive cNTS neurons. The population of somatic/dendritic nAChRs has been found to be heterogeneous and included nAChRs that were activated by RJR-2403 and/or cytisine, or insensitive to cytisine, or inhibited by MLA. The presented results are consistent with the expression of β4-containing (i.e., β4*) nAChRs, likely α3β4*, in pre-synaptic terminals of effect-positive cNTS neurons. Somatic/dendritic nAChRs appear to involve both α7 and non-α7 subunits. Heterogeneity in the subunit composition of pre-synaptic and somatic/dendritic nAChRs may underlie diverse roles that these receptors play in regulation of behavioral and visceral reflexes, and may reflect specific targeting by endogenous nicotinic agents and nicotine.