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Serotonin (5-hydroxytryptamine, 5-HT) controls pyramidal cell activity in prefrontal cortex (PFC) through various receptors, in particular, 5-HT 1A  and 5-HT 2A  receptors. Here we report that the physiological stimulation of the raphe nuclei excites local, putatively GABAergic neurons in the prelimbic and cingulate areas of the rat PFC  in vivo . These excitations had a latency of 36 ± 4 ms and a duration of 69 ± 9 ms and were blocked by the i.v. administration of the 5-HT 3  receptor antagonists ondansetron and tropisetron. The latency and duration were shorter than those elicited through 5-HT 2A  receptors in pyramidal neurons of the same areas. Double  in situ  hybridization histochemistry showed the presence of GABAergic neurons expressing 5-HT 3  receptor mRNA in PFC. These cells were more abundant in the cingulate, prelimbic and infralimbic areas, particularly in superficial layers. The percentages of GAD mRNA-positive neurons expressing 5-HT 3  receptor mRNA in prelimbic cortex were 40, 18, 6 and 8% in layers I, II–III, V and VI, respectively, a distribution complementary to that of cells expressing 5-HT 2A  receptors. Overall, these results support an important role of 5-HT in the control of the excitability of apical dendrites of pyramidal neurons in the medial PFC through the activation of 5-HT 3  receptors in GABAergic interneurons.

In Vivo Excitation of GABA Interneurons in the Medial Prefrontal Cortex through 5-HT 3 Receptors