Nitric oxide signaling exerts bidirectional effects on plasticity inductions in amygdala

It has been well known that long-term potentiation (LTP) of synaptic transmission in the lateral nucleus of the amygdala (LA) constitutes an essential cellular mechanism contributing to encoding of conditioned fear. Nitric oxide (NO), produced by activation of the postsynaptic N-methyl-D-aspartate receptors (NMDAR) in thalamic input to the LA, has been thought to promote LTP, contributing to the establishment of conditioned fear. However, it is not known whether and how NO, released from cortical input to the LA, plays the role on the plasticity induction and fear memory. Here we report that the diffusion of NO, released in response to activation of presynaptic NMDAR on cortical afferent fibers in the LA, could suppress heterosynaptically a form of presynaptic kainate receptor (KAR) dependent LTP (pre-LTP) in thalamic input, which was induced by low-frequency presynaptic stimuli without postsynaptic depolarization. We also confirmed that NO, produced by activation of postsynaptic NMDAR in thalamic input, can promote postsynaptic NMDAR-dependent LTP (post-LTP), which was induced by pairing protocol. These LTPs were occluded following fear conditioning, indicating that they could contribute to encoding of conditioned fear memory. However, their time courses are different; Post-LTP was more rapidly formed than pre-LTP in the course of fear conditioning. NO, produced by activation of presynaptic NMDAR in cortical input and postsynaptic NMDAR in thalamic input, may control conditioned fear by suppressing pre-LTP and promoting post-LTP, respectively, in thalamic input to the LA.