Long-term depression in the basolateral amygdala of the mouse involves the activation of interneurons.

Long-term depression (LTD) in the basolateral amygdala, following low frequency stimulation (1 Hz/900 pulses) of the lateral amygdala, was studied in an in vitro slice preparation of 2-3 weeks and 2-4 months old mice. Whole-cell patch-clamp recordings of neurons, visualized by means of infrared videomicroscopy, and extracellular field potential recordings were performed. Loading single neurons with the calcium chelator BAPTA (30 mM) did not reduce the excitatory postsynaptic currents following low frequency stimulation. However, buffering presynaptic calcium with BAPTA-AM, and application of the specific Ca2+/calmodulin-stimulated protein kinase II antagonist KN-62 (1-[N,O-bis(5-isoquinoline sulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperizine), blocked low frequency stimulation-induced LTD. The induction of LTD was reduced by the competitive N-methyl-D-aspartate receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (50 microM), and blocked by the metabotropic glutamate receptor antagonist (-)-amino-4-carboxy-methyl-phenylacetic acid (1 mM), and by 5-hydroxytryptamine (5-HT; 30 microM) via the activation of 5-HT(1A) receptors. Also blocking GABA(A) receptor-mediated synaptic transmission with bicuculline (10 microM) or picrotoxin (20 microM) reduced the induction of LTD. Visually and electrophysiologically identified interneurons in slices from 2 weeks old mice, expressed in contrast to adult mice (2-4 months), pronounced LTD. Principal neurons showed only weak LTD after low frequency stimulation.A synopsis of these findings suggests a pivotal role of GABAergic interneurons and serotonergic afferents in the induction of LTD in the basolateral nucleus of the amygdala.