Synaptic plasticity and NO-cGMP-PKG signaling regulate pre- and postsynaptic alterations at rat lateral amygdala synapses following fear conditioning.
In vertebrate models of synaptic plasticity, signaling via the putative "retrograde messenger" nitric oxide (NO) has been hypothesized to serve as a critical link between functional and structural alterations at pre- and postsynaptic sites. In the present study, we show that auditory Pavlovian fear conditioning is associated with significant and long-lasting increases in the expression of the postsynaptically-localized protein GluR1 and the presynaptically-localized proteins synaptophysin and synapsin in the lateral amygdala (LA) within 24 hrs following training. Further, we show that rats given intra-LA infusion of either the NR2B-selective antagonist Ifenprodil, the NOS inhibitor 7-Ni, or the PKG inhibitor Rp-8-Br-PET-cGMPS exhibit significant decreases in training-induced expression of GluR1, synaptophysin, and synapsin immunoreactivity in the LA, while those rats infused with the PKG activator 8-Br-cGMP exhibit a significant increase in these proteins in the LA. In contrast, rats given intra-LA infusion of the NO scavenger c-PTIO exhibit a significant decrease in synapsin and synaptophysin expression in the LA, but no significant impairment in the expression of GluR1. Finally, we show that intra-LA infusions of the ROCK inhibitor Y-27632 or the CaMKII inhibitor KN-93 impair training-induced expression of GluR1, synapsin, and synaptophysin in the LA. These findings suggest that the NO-cGMP-PKG, Rho/ROCK, and CaMKII signaling pathways regulate fear memory consolidation, in part, by promoting both pre- and post-synaptic alterations at LA synapses. They further suggest that synaptic plasticity in the LA during auditory fear conditioning promotes alterations at presynaptic sites via NO-driven "retrograde signaling".
Ota
Kristie T
KT
Department of Psychology, Yale University, New Haven, Connecticut, USA.
Monsey
Melissa S
MS
Wu
Melissa S
MS
Schafe
Glenn E
GE
D000679:Amygdala / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003213:Conditioning, Psychological; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D005239:Fear; D005786:Gene Expression Regulation; D008297:Male; D009473:Neuronal Plasticity; D009569:Nitric Oxide / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D006152:Cyclic GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D009569:Nitric Oxide; D018091:Receptors, AMPA; D016704:Synapsins; D016708:Synaptophysin; D054460:rho-Associated Kinases