Bidirectional regulations for glutamate and GABA release in the hippocampus by α7 and non-α7 ACh receptors

Abstract

In the assay of glutamate and γ-aminobutyric acid (GABA) with a high-performance liquid chromatography, spontaneous release of glutamate and GABA from rat hippocampal slices was significantly enhanced by mecamylamine, an inhibitor of non-α7 ACh receptors, or α-bungarotoxin, an inhibitor of α7 ACh receptors in the absence of tetrodotoxin (TTX), but not in the presence of TTX. Nicotine significantly enhanced glutamate and GABA release in the absence of TTX, that is abolished by mecamylamine or α-bungarotoxin, while it had no effect on the release in the presence of TTX. In the recording of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (AMPA-EPSCs) and GABA A receptor-mediated inhibitory postsynaptic currents (GABA A-IPSCs) from CA1 pyramidal neurons of rat hippocampal slices, nicotine did not affect the rate and amplitude of AMPA-EPSCs and AMPA-miniature EPSCs. In contrast, nicotine significantly increased the rate of GABA A-IPSCs, without affecting the amplitude, but such effect was not obtained with GABA A-miniature IPSCs. The collective results suggest that α7 and non-α7 ACh receptors expressed in the hippocampus, activated under the basal conditions, inhibit release of glutamate and GABA controlled through multi-synaptic relays, but that otherwise, those receptors, highly activated by nicotine, stimulate both the release, with a part of GABA released from interneurons transmitting to CA1 pyramidal neurons. Furthermore, the results also suggest that α7 and non-α7 ACh receptors do not have potency sufficiently to modulate glutamate and GABA release controlled by single synapses.