title: Activation of 5-HT receptors inhibits GABAergic transmission by pre-and post-synaptic mechanisms in layer II/III of the juvenile rat auditory cortex.
abstract: The specific mechanisms by which serotonin (5-HT) modulates synaptic transmission in the auditory cortex are still unknown. In this work, we used whole-cell recordings from layer II/III of pyramidal neurons in rat brain slices to characterize the influence of 5-HT on inhibitory synaptic activity in the auditory cortex after pharmacological blockade of excitatory glutamatergic transmission. We found that bath application of 5-HT (5 µM) reduced the frequency and amplitude of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs), reduced the amplitude of evoked IPSCs, and enhanced facilitation of paired pulse ratio (PPR), suggesting presynaptic inhibition. To determine which the serotonin receptors were involved in this effect, we studied the influence of specific 5-HT receptor agonists and antagonists on ɣ-aminobutyric acid (GABA)ergic synaptic transmission. The inhibiting influence of 5-HT in the GABAergic synaptic activity was mimicked by using the selective agonists of the 5-HT1A and 5-HT2A receptors, 8(OH)-DPAT (10 µM) and DOI (10 µM), respectively; and it was prevented by their respective antagonists NAN-190 (1 µM) and ritanserin (1 μM). Furthermore, the application of the selective agonist of 5-HT1A receptors, 8-(OH)-DPAT (10 µM), produced PPR facilitation, while DOI application (5-HT2A agonist) did not change the PPR. Moreover, the 5-HT2A agonist reduced the amplitude of the IPSCs evoked by application of the selective GABA agonist, muscimol. These results suggest a presynaptic and postsynaptic reduction of GABAergic transmission mediated by 5-HT1A and 5-HT2A serotonergic receptors, respectively.
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, Texas; Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas, Texas.
authors.forename: Francisco
authors.initials: F
authors.lastname: García-Oscos
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Torres-Ramírez
authors.forename: Lu
authors.initials: L
authors.lastname: Dinh
authors.forename: Luis
authors.initials: L
authors.lastname: Galindo-Charles
authors.forename: Elsy Arlene
authors.initials: EA
authors.lastname: Pérez Padilla
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Pineda
authors.forename: Marco
authors.initials: M
authors.lastname: Atzori
authors.forename: Humberto
authors.initials: H
authors.lastname: Salgado
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001303:Auditory Cortex / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials; D055369:Miniature Postsynaptic Potentials; D009118:Muscimol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D016713:Ritanserin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D000662:Amphetamines; D018755:GABA Agonists; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D016713:Ritanserin; D009118:Muscimol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: 5-HT receptors; GABA release; GABAA receptors; auditory cortex; cortical circuitry; whole-cell