5-HT receptors enhance inhibitory synaptic input to principal neurons in the mouse basal amygdala.

The basal amygdala (BA) has been implicated in encoding fear and its extinction. The level of serotonin (5-HT) in the BA increases due to arousal and stress related to aversive stimuli. The effects of 5-HT receptor (5-HTR) activation and blockade on the activity of BA neurons have not yet been investigated. In the present study, a transgenic mouse line carrying green fluorescent protein (GFP) reporter gene was used to identify neurons that express the 5-HTR. GFP immunoreactivity was present mainly in cells that also expressed GAD67 or parvalbumin (PV), the phenotypic markers for GABAergic interneurons. Most cells showing GFP fluorescence demonstrated firing patterns characteristic of BA inhibitory interneurons. Activation of 5-HTRs resulted in a depolarization and/or occurrence of spontaneous spiking activity of BA interneurons that was accompanied by an increase in the mean frequency and mean amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from BA principal neurons. These effects were blocked by a specific 5-HTR antagonist, SB269970 and were absent in slices from 5-HTR knockout mice. Activation of 5-HTRs also decreased the mean frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from BA principal neurons, which was blocked by the GABA receptor antagonist picrotoxin. Neither inhibitory nor excitatory miniature postsynaptic currents (mIPSCs/mEPSCs) were affected by 5-HTR activation. These results show that in the BA 5-HTRs stimulate an activity-dependent enhancement of inhibitory input from local interneurons to BA principal neurons and provide insights about the possible involvement of BA serotonergic receptors in neuronal mechanisms underlying fear memory.