Serotonin 5‐ HT 1B receptor‐mediated calcium influx‐independent presynaptic inhibition of GABA release onto rat basal forebrain cholinergic neurons

Modulatory roles of serotonin (5‐ HT ) in GABA ergic transmission onto basal forebrain cholinergic neurons were investigated, using whole‐cell patch‐clamp technique in the rat brain slices. GABA A receptor‐mediated inhibitory postsynaptic currents ( IPSC s) were evoked by focal stimulation. Bath application of 5‐ HT (0.1–300 μ m ) reversibly suppressed the amplitude of evoked IPSC s in a concentration‐dependent manner. Application of a 5‐ HT 1B receptor agonist, CP 93129, also suppressed the evoked IPSC s, whereas a 5‐ HT 1A receptor agonist, 8‐ OH ‐ DPAT had little effect on the evoked IPSC s amplitude. In the presence of NAS ‐181, a 5‐ HT 1B receptor antagonist, 5‐ HT ‐induced suppression of evoked IPSC s was antagonised, whereas NAN ‐190, a 5‐ HT 1A receptor antagonist did not antagonise the 5‐ HT ‐induced suppression of evoked IPSC s. Bath application of 5‐ HT reduced the frequency of spontaneous miniature IPSC s without changing their amplitude distribution. The effect of 5‐ HT on miniature IPSC s remained unchanged when extracellular Ca 2+ was replaced by Mg 2+ . The paired‐pulse ratio was increased by CP 93129. In the presence of ω‐Cg TX , the N‐type Ca 2+ channel blocker, ω‐Aga‐ TK , the P/Q‐type Ca 2+ channel blocker, or SNX ‐482, the R‐type Ca 2+ channel blocker, 5‐ HT could still inhibit the evoked IPSC s. 4‐ AP , a K + channel blocker, enhanced the evoked IPSC s, and CP 93129 had no longer inhibitory effect in the presence of 4‐ AP . CP 93129 increased the number of action potentials elicited by depolarising current pulses. These results suggest that activation of presynaptic 5‐ HT 1B receptors on the terminals of GABA ergic afferents to basal forebrain cholinergic neurons inhibits GABA release in Ca 2+ influx‐independent manner by modulation of K + channels, leading to enhancement of neuronal activities.