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PMID:10381597

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Citation

Koyama, S, Kubo, C, Rhee, JS and Akaike, N (1999) Presynaptic serotonergic inhibition of GABAergic synaptic transmission in mechanically dissociated rat basolateral amygdala neurons. J. Physiol. (Lond.) 518 ( Pt 2):525-38

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-HT1A specific agonist 8-OH DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) and blocked by the 5-HT1A 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-HT1A receptor and this intracellular pathway directly acts on the GABA-releasing process independent of K+ and Ca2+ channels in the presynaptic nerve terminals.

Links

PubMed PMC2269437

Keywords

Adenylyl Cyclases/drug effects; Adenylyl Cyclases/physiology; Amygdala/cytology; Amygdala/drug effects; Amygdala/physiology; Animals; Cadmium/pharmacology; Excitatory Postsynaptic Potentials/physiology; In Vitro Techniques; Male; Neurons/drug effects; Neurons/physiology; Patch-Clamp Techniques; Potassium/pharmacology; Raphe Nuclei/cytology; Raphe Nuclei/drug effects; Raphe Nuclei/physiology; Rats; Rats, Wistar; Receptors, Presynaptic/drug effects; Receptors, Serotonin/drug effects; Receptors, Serotonin, 5-HT1; Ruthenium Red/pharmacology; Serotonin/pharmacology; Serotonin Antagonists/pharmacology; Serotonin Receptor Agonists/pharmacology; Signal Transduction/drug effects; Synaptic Transmission/drug effects; Synaptic Transmission/physiology; gamma-Aminobutyric Acid/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:5HT1A

part_of

GO:0098982: GABA-ergic synapse

ECO:0006013: patch-clamp recording evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:5HT1A

part_of

GO:0098982: GABA-ergic synapse

ECO:0006054: pharmacological assay evidence used in manual assertion

C

  • part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:5HT1A

part_of

GO:0098982: GABA-ergic synapse

ECO:0006013: patch-clamp recording evidence used in manual assertion

C

part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:5HT1A

part_of

GO:0098982: GABA-ergic synapse

ECO:0006054: pharmacological assay evidence used in manual assertion

C

part_of:(UBERON:0002421)

Seeded From UniProt

complete

RAT:5HT1A

part_of

GO:0099056: integral component of presynaptic membrane

ECO:0006013: patch-clamp recording evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:5HT1A

part_of

GO:0099056: integral component of presynaptic membrane

ECO:0006054: pharmacological assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:5HT1A

involved_in

GO:2000300: regulation of synaptic vesicle exocytosis

ECO:0006013: patch-clamp recording evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:5HT1A

involved_in

GO:2000300: regulation of synaptic vesicle exocytosis

ECO:0006054: pharmacological assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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