title: Synaptic plasticity and NO-cGMP-PKG signaling regulate pre- and postsynaptic alterations at rat lateral amygdala synapses following fear conditioning.
abstract: 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".
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut, USA.
authors.forename: Kristie T
authors.initials: KT
authors.lastname: Ota
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Monsey
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Wu
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Schafe
mesh_terms: 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
chemical_list: 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