Long-term potentiation at excitatory synaptic inputs to the intercalated cell masses of the amygdala

The intercalated cell masses (ITCs) of the amygdala are clusters of GABAergic interneurons that surround the basolateral complex of the amygdala. ITCs have been increasingly implicated in the acquisition and extinction of conditioned fear responses, but the underlying cellular mechanisms remain unexplored. Here, we report that repetitive stimulation of lateral amygdala (LA) afferents with a modified theta burst stimulation (TBS) protocol and induces long-term potentiation (LTP) of excitatory synapses onto medial paracapsular ITC (Imp) neurons. This TBS-induced LTP is; (1) induced and expressed post-synaptically, (2) involves a rise in post-synaptic Ca²⁺ and the activation of NR2B-containing N-methyl-D-aspartate receptors (NMDARs), (3) dependent on calcium/calmodulin-dependent protein kinase II and cAMP-dependent protein kinase activation, and (4) associated with increased exocytotic delivery of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) to the post-synaptic membrane. Remarkably, auditory fear conditioning led to a persistent increase in AMPAR/NMDAR ratio of glutamatergic synaptic currents and occluded TBS-induced LTP at LA-Imp synapses. Furthermore, extinction training rescued the effect of fear conditioning on AMPAR/NMDAR ratio and LTP induction. These results show that a prominent form of LTP can be elicited at LA-Imp synapses and suggest that this synaptic plasticity may contribute to the expression of fear conditioning.