Presynaptic serotonergic inhibition of GABAergic synaptic transmission in mechanically dissociated rat basolateral amygdala neurons

Susumu Koyama, Chiharu Kubo, Jeong Seop Rhee, Norio Akaike

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

1. The basolateral amygdala (ABL) nuclei contribute to the process of anxiety. GABAergic transmission is critical in these nuclei and serotonergic inputs from dorsal raphe nuclei also significantly regulate GABA release. In mechanically dissociated rat ABL neurons, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) arising from attached GABAergic presynaptic nerve terminals were recorded with the nystatin-perforated patch method and pharmacological isolation. 2. 5-HT reversibly reduced the GABAergic mIPSC frequency without affecting the mean amplitude. The serotonergic effect was mimicked by the 5-HT(1A) specific agonist 8-OH DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) and blocked by the 5-HT(1A) antagonist spiperone. 3. The GTP-binding protein inhibitor N-ethylmaleimide removed the serotonergic inhibition of mIPSC frequency. In either K+-free or Ca2+-free external solution, 5-HT could inhibit mIPSC frequency. 4. High K+ stimulation increased mIPSC frequency and 8-OH DPAT inhibited this increase even in the presence of Cd2+. 5. Forskolin, an activator of adenylyl cyclase (AC), significantly increased synaptic GABA release frequency. Pretreatment with forskolin prevented the serotonergic inhibition of mIPSC frequency in both the standard and high K+ external solution. 6. Ruthenium Red (RR), an agent facilitating the secretory process in a Ca2+-independent manner, increased synaptic GABA release. 5-HT also suppressed RR-facilitated mIPSC frequency. 7. We conclude that 5-HT inhibits GABAergic mIPSCs by inactivating the AC-cAMP signal transduction pathway via a G-protein-coupled 5-HT(1A) receptor and this intracellular pathway directly acts on the GABA-releasing process independent of K+ and Ca2+ channels in the presynaptic nerve terminals.

Original languageEnglish
Pages (from-to)525-538
Number of pages14
JournalJournal of Physiology
Volume518
Issue number2
DOIs
Publication statusPublished - Jul 15 1999

All Science Journal Classification (ASJC) codes

  • Physiology

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