Activation of 5‐ HT receptors inhibits GABA ergic transmission by pre‐and post‐synaptic mechanisms in layer II/III of the juvenile rat auditory cortex

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‐HT 1A and 5‐HT 2A 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‐HT 1A receptors, 8‐(OH)‐DPAT (10 µM), produced PPR facilitation, while DOI application (5‐HT 2A agonist) did not change the PPR. Moreover, the 5‐HT 2A 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‐HT 1A and 5‐HT 2A serotonergic receptors, respectively. Synapse 69:115–127, 2015. © 2014 Wiley Periodicals, Inc.