Synaptic plasticity and NO-cGMP-PKG signaling coordinately regulate ERK-driven gene expression in the lateral amygdala and in the auditory thalamus following Pavlovian fear conditioning.
We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the present series of experiments, we show that N-methyl-D-aspartate receptor (NMDAR)-driven synaptic plasticity and NO-cGMP-PKG signaling in the LA regulate the training-induced expression of ERK and the ERK-driven immediate early genes (IEGs) Arc/Arg3.1, c-Fos, and EGR-1 in the LA and the MGm/PIN. Rats receiving intra-LA infusion of the NR2B selective antagonist Ifenprodil, the NOS inhibitor 7-Ni, or the PKG inhibitor Rp-8-Br-PET-cGMPS exhibited significant decreases in ERK activation and in the training-induced expression of all three IEGs in the LA and MGm/PIN while intra-LA infusion of the PKG activator 8-Br-cGMP had the opposite effect. Remarkably, those rats given intra-LA infusion of the membrane impermeable NO scavenger c-PTIO exhibited significant decreases in ERK activation and ERK-driven IEG expression in the MGm/PIN, but not in the LA. Together with our previous experiments, these results suggest that synaptic plasticity and the NO-cGMP-PKG signaling pathway promote fear memory consolidation, in part, by regulating ERK-driven transcription in both the LA and the MGm/PIN. They further suggest that synaptic plasticity in the LA during fear conditioning promotes ERK-driven transcription in MGm/PIN neurons via NO-driven "retrograde signaling."
Ota
Kristie T
KT
Department of Psychology, Yale University, New Haven, Connecticut 06520, USA.
Monsey
Melissa S
MS
Wu
Melissa S
MS
Young
Grace J
GJ
Schafe
Glenn E
GE
D000161:Acoustic Stimulation / Q000009:adverse effects; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005239:Fear / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D017869:Cyclic GMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D006152:Cyclic GMP