NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR ACTIVATION MODULATES GAMMA-AMINOBUTYRIC-ACID RELEASE FROM CA1 NEURONS OF RAT HIPPOCAMPAL SLICES

In the present study we investigated electrophysiologically the nicoti nic responses of pyramidal neurons and interneurons visualized by infr ared-assisted videomicroscopy and fluorescence in the CAI field of hip pocampal slices obtained from 8- to 24-day-old rats. Application of ni cotinic agonists to CA1 neurons evoked at least four types of nicotini c responses. Of major interest was the ability of these agonists to in duce the release of gamma-aminobutyric acid (GABA) from interneurons. Slowly decaying ACh whole-cell currents and GABA-mediated postsynaptic currents could be recorded from pyramidal neurons and interneurons, w hereas fast-decaying nicotinic currents and fast current transients we re recorded only from interneurons. Nicotinic responses were sensitive to blockade by d-tubocurarine (10 mu M), which indicated that they we re mediated by nicotinic acetylcholine receptors (nAChRs). The slowly decaying currents, the postsynaptic currents and the fast current tran sients were insensitive to blockade by the alpha-7 nAChR-specific anta gonist methyllycaconitine (up to 1 mu M) or alpha-bungarotoxin (100 nM ). On the other hand, the slowly decaying nicotinic currents recorded from the interneurons were blocked by the alpha 4 beta 2 nAChR-specifi c antagonist dihydro-beta-erythroidine, and the fast-desensitizing nic otinic currents were evoked by the alpha-7 nAChR-specific agonist chol ine. In experimental conditions similar to those used to record nicoti nic responses from neurons in slice (i.e., in the absence of tetrodoto xin), we observed that nicotinic agonists can also induce the release of GABA from hippocampal neurons in culture. In summary, these results provide direct evidence for more than one subtype of functional nAChR in CA1 neurons and suggest that activation of nAChRs present in GABAe rgic interneurons can evoke inhibitory activity in CA? pyramidal neuro ns, thereby modulating processing of information in the hippocampus.