Synaptic plasticity and NO-cGMP-PKG signaling regulate pre- and postsynaptic alterations at rat lateral amygdala synapses following fear conditioning

PLoS One. 2010 Jun 21;5(6):e11236. doi: 10.1371/journal.pone.0011236.

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".

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amygdala / cytology*
  • Amygdala / metabolism
  • Amygdala / physiology*
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Conditioning, Psychological*
  • Cyclic GMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Fear*
  • Gene Expression Regulation
  • Male
  • Neuronal Plasticity*
  • Nitric Oxide / metabolism
  • Protein Transport
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism
  • Signal Transduction*
  • Synapses / metabolism*
  • Synapsins / metabolism
  • Synaptophysin / metabolism
  • rho-Associated Kinases / metabolism

Substances

  • Receptors, AMPA
  • Synapsins
  • Synaptophysin
  • Nitric Oxide
  • rho-Associated Kinases
  • Cyclic GMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Cyclic GMP
  • glutamate receptor ionotropic, AMPA 1