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The Journal of Neuroscience, September 1, 2002, 22(17):7509-7517

Activation of Presynaptic 5-Hydroxytryptamine 2A Receptors Facilitates Excitatory Synaptic Transmission via Protein Kinase C in the Dorsolateral Septal Nucleus

Hiroshi Hasuo¹, Toshimasa Matsuoka^{1, 2}, and Takashi Akasu¹

Departments of ¹ Physiology and ² Neuropsychiatry, Kurume University School of Medicine, Kurume 830-0011, Japan

Effects of 5-hydroxytryptamine (5-HT) on EPSPs and EPSCs in the rat dorsolateral septal nucleus (DLSN) were examined in the presence of GABA_A and GABA_B receptor antagonists. Bath application of 5-HT (10 µM) for 5-10 min increased the amplitude of the EPSP and EPSC. (±)-8-Hydroxy-2-(di-N-propylamino)tetralin hydrobromide (10 µM), an agonist for 5-HT_1A and 5-HT₇ receptors, did not facilitate the EPSP. -Methyl-5-HT (10 µM), a 5-HT₂ receptor agonist, increased the amplitude of the EPSC. -Methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (10 µM) and 6-chloro-2-(1-piperazinyl)pyrazine (10 µM), selective 5-HT_2B and 5-HT_2C receptor agonists, respectively, had no effect on the EPSP. The 5-HT-induced facilitation of the EPSP was blocked by ketanserin (10 µM), a 5-HT_2A/2C receptor antagonist. However, N-desmethylclozapine (10 µM), a selective 5-HT_2C receptor antagonist, did not block the facilitation of the EPSP induced by -methyl-5-HT. The inward current evoked by exogenous glutamate was unaffected by 5-HT. 5-HT (10 µM) and -methyl-5-HT (10 µM) increased the frequency of miniature EPSPs (mEPSPs) without changing the mEPSP amplitude. The ratio of the paired pulse facilitation was significantly decreased by 5-HT and -methyl-5-HT. The 5-HT-induced facilitation of the EPSP was blocked by calphostin C (100 nM), a specific protein kinase C (PKC) inhibitor, but not by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (10 µM), a protein kinase A inhibitor. Phorbol 12,13-dibutyrate (3 µM) mimicked the facilitatory effects of 5-HT. These results suggest that 5-HT enhances the EPSP by increasing the release of glutamate via presynaptic 5-HT_2A receptors that link with PKC in rat DLSN neurons.

Key words: rat; dorsolateral septal nucleus; EPSP; mEPSP; paired pulse facilitation; 5-HT_2A receptor; synaptic facilitation; PKC; G-protein

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22177509-09$05.00/0

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