Serotonergic control of GABAergic inhibition in the lateral amygdala

Much evidence implicates the serotonergic regulation of the amygdala in anxiety. Thus the present study was undertaken to characterize the influence of serotonin (5-HT) on principal neurons (PNs) of the rat lateral amygdala (LA), using whole cell recordings in vitro. Because inhibition is a major determinant of PN activity, we focused on the control of GABAergic transmission by 5-HT. IPSCs were elicited by local electrical stimulation of LA in the presence of glutamate receptor antagonists. We found that 5-HT reduces GABA_A inhibitory postsynaptic currents (IPSCs) via presynaptic 5-HT_1B receptors. While the presynaptic inhibition of GABA release also attenuated GABA_B currents, this effect was less pronounced than for GABA_A currents because 5-HT also induced a competing postsynaptic enhancement of GABA_B currents. That is, GABA_B currents elicited by pressure application of GABA or baclofen were enhanced by 5-HT. In addition, we obtained evidence suggesting that 5-HT differentially regulates distinct subsets of GABAergic synapses. Indeed, GABA_A IPSCs were comprised of two components: a relatively 5-HT-insensitive IPSC that had a fast time course and a 5-HT-sensitive component that had a slower time course. Because the relative contribution of these two components varied depending on whether neurons were recorded at proximity versus at a distance from the stimulating electrodes, we speculate that distinct subtypes of local-circuit cells contribute the two contingents of GABAergic synapses. Overall, our results indicate that 5-HT is a potent regulator of synaptic inhibition in LA.NEW & NOTEWORTHY We report that 5-HT, acting via presynaptic 5-HT_1B receptors, attenuates GABA_A IPSCs by reducing GABA release in the lateral amygdala (LA). In parallel, 5-HT enhances GABA_B currents postsynaptically, such that GABA_B inhibitory postsynaptic currents (IPSCs) are relatively preserved from the presynaptic inhibition of GABA release. We also found that the time course of 5-HT-sensitive and -insensitive GABA_A IPSCs differ. Together, these results indicate that 5-HT is a potent regulator of synaptic inhibition in LA.