Choline and selective antagonists identify two subtypes of nicotinic acetylcholine receptors that modulate GABA release from CA1 interneurons in rat hippocampal slices

Neuronal nicotinic receptors (nAChR) are known to control transmitter relea se in the CNS. Thus, this study was aimed at exploring the diversity and lo calization of nAChRs present in CA1 interneurons in rat hippocampal slices. The use of a U-tube as the agonist delivery system was critical for the re liable detection of nicotinic responses induced by brief exposure of the ne urons to ACh or to the alpha 7 nAChR-selective agonist choline. The present study demonstrated that CA1 interneurons, in addition to expressing functi onal alpha 7 nAChRs, also express functional alpha 4 beta 2-like nAChRs and that activation of both receptors facilitates an action potential-dependen t release of GABA. Depending on the experimental condition, one of the foll owing nicotinic responses was recorded from the interneurons by means of th e patch-damp technique: a nicotinic whole-cell current, depolarization acco mpanied by action potentials, or GABA-mediated postsynaptic currents (PSCs) . Responses mediated by alpha 7 nAChRs were short-lasting, whereas those me diated by alpha 4 beta 2 nAChRs were long-lasting. Thus, phasic or tonic in hibition of CAI interneurons may be achieved by selective activation of alp ha 7 or alpha 4 beta 2 nAChRs, respectively. It can also be suggested that synaptic levels of choline generated by hydrolysis of ACh in vivo may be su fficient to control the activity of the alpha 7 nAChRs. The finding that me thyllycaconitine and dihydro-P-erythroidine (antagonists of alpha 7 and alp ha 4 beta 2 nAChRs, respectively) increased the frequency and amplitude of GABAergic PSCs suggests that there is an intrinsic cholinergic activity tha t sustains a basal level of nAChR activity in these interneurons.