A Specific Class of Interneuron Mediates Inhibitory Plasticity in the Lateral Amygdala

Abstract

The lateral amygdala (LA) plays a key role in emotional learning and is the main site for sensory input into the amygdala. Within the LA, pyramidal neurons comprise the major cell population with plasticity of inputs to these neurons thought to underlie fear learning. Pyramidal neuron activity is tightly controlled by local interneurons, and GABAergic modulation strongly influences amygdaladependent learning. Synaptic inputs to some interneurons in the LA can also undergo synaptic plasticity, but the identity of these cells and the mechanisms that underlie this plasticity are not known. Here we show that long-term potentiation (LTP) in LA interneurons is restricted to a specific type of interneuron that is defined by the lack of expression of synaptic NR2B subunits. We find that LTP is only present at cortical inputs to these cells and is initiated by calcium influx via calcium-permeable AMPA receptors. LTP is maintained by trafficking of GluR2-lacking AMPA receptors that require an interaction with SAP97 and the actin cytoskeleton. Our results define a novel population of interneurons in the LA that control principal neuron excitability by feed-forward inhibition of cortical origin. This selective enhanced inhibition may contribute to reducing the activity of principal neurons engaged during extinction of conditioned fear.

Synaptic NMDA receptors in basolateral amygdala principal neurons are triheteromeric proteins: physiological role of GluN2B subunits

“…Both GluN2A and GluN2B subunits are expressed in the adult BLA (Farb et al 1995;Lopez de Armentia and Sah 2003). Although GluN3 subunits are expressed in the amygdala, receptors containing these subunits show greatly reduced magnesium sensitivity (Chatterton et al 2002) and are unlikely to be present at synapses in BLA neurons as synaptic NMDA receptors in both principal neurons Mahanty and Sah 1999) and interneurons (Polepalli et al 2010) show normal magnesium sensitivity. To understand the subunit composition of synaptic NMDA receptors in the BLA, we first determined the expression of GluN1, GluN2A, and GluN2B subunits using subcellular fractionation and Western blot.…”

Pituitary Adenylate Cyclase-Activating Polypeptide Induces Postsynaptically Expressed Potentiation in the Intra-amygdala Circuit

“…3 A , C ), suggested to us that postsynaptic trafficking of GluR1 subunit-containing AMPA receptor to the sites of synaptic transmission could contribute to PACAP-induced synaptic strengthening (Hayashi et al, 2000). To explore this possibility, we loaded postsynaptic CeL neurons with Pep1-TGL (200 μM), a synthetic peptide which corresponds to the C-terminus of the AMPA receptor GluR1 subunit and inhibits the delivery of GluR1-containing AMPA receptors to the postsynaptic sites by disrupting the interaction of GluR1 C-terminus with the synapse-associated protein SAP97 (Lin et al, 2010; Polepalli et al, 2010; Hayashi et al, 2000; Shi et al, 2001; Yang et al, 2008). This experimental intervention resulted in a suppression of PACAP38-induced potentiation, with the EPSC amplitude remaining at 107 % ± 5 % of the baseline value (Fig.…”

Synaptic competition in the lateral amygdala and the stimulus specificity of conditioned fear: a biophysical modeling study

“…On the input side, it was reported that both thalamic and cortical inputs onto ITNs of LA can undergo activity-dependent long-term potentiation (LTP; Mahanty and Sah 1998; Szinyei et al 2000; Bauer and LeDoux 2004; Polepalli et al 2010). In particular, a form of AMPA-dependent LTP was reported as some ITNs express Ca 2+ -permeable AMPA receptors because they lack the GluR2 receptor subunit (Mahanty and Sah 1998; Szinyei et al 2000; Polepalli et al 2010). On the output side, it was also shown that ITN synapses onto PNs can undergo activity-dependent plasticity via a Ca 2+ -dependent mechanism (Bauer and LeDoux 2004).…”