Signaling through cGMP-Dependent Protein Kinase I in the Amygdala Is Critical for Auditory-Cued Fear Memory and Long-Term Potentiation

Abstract

Long-term potentiation (LTP) of inputs relaying sensory information from cortical and thalamic neurons to principal neurons in the lateral amygdala (LA) is thought to serve as a cellular mechanism for associative fear learning. Nitric oxide (NO), a messenger molecule widely implicated in synaptic plasticity and behavior, has been shown to enhance LTP in the LA as well as consolidation of associative fear memory. Additional evidence suggests that NO-induced enhancement of LTP and amygdala-dependent learning requires signaling through soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinase (cGK). Mammals possess two genes for cGK: the prkg1 gene gives rise to the cGK type I isoforms, cGKI␣ and cGKI␤, and the prkg2 gene encodes the cGK type II. Reportedly, both cGKI and cGKII are expressed in the amygdala, and cGKII is involved in controlling anxiety-like behavior. Because selective pharmacological tools for individual cGK isoforms are lacking, we used different knock-out mouse models to examine the function of cGKI and cGKII for LTP in the LA and pavlovian fear conditioning. We found robust expression of the cGKI specifically in the LA with cGKI␤ as the prevailing isoform. We further show a marked reduction of LTP at both thalamic and cortical inputs to the LA and a selective impairment of auditory-cued fear memory in cGKI-deficient mutants. In contrast, cGKII null mutants lack these phenotypes. Our data suggest a function of cGKI, likely the ␤ isoform, in the LA, supporting synaptic plasticity and consolidation of fear memory.

The roles of protein kinases in learning and memory

“…There are two PKG isoforms encoded by different genes. Neuronal KO of isoform I (cGKI) results in specific impairment in cued fear LTM formation (Paul et al 2008). These cGKI KO mice are not deficient in cued fear STM and contextual fear LTM.…”

The visual orientation memory of Drosophila requires Foraging (PKG) upstream of Ignorant (RSK2) in ring neurons of the central complex

“…(Feil et al 2003). Furthermore, mice lacking PKG in the amygdala exhibit an impairment in fear conditioning (Paul et al 2008) and cGMP/PKG signaling in the hippocampus is required for novel object recognition (Feil et al 2009). In insects, FOR is involved in different types of food searching behavior and associative memories in which establishing the learning traces takes at least seconds (Reaume and Sokolowski 2009).…”

Gene–environment interplay inDrosophila melanogaster: Chronic food deprivation in early life affects adult exploratory and fitness traits

“…In D. melanogaster, for is known to have important effects on a number of traits, including sleep (21) and memory (22). PRKG1, the mammalian homolog of PKG, is implicated in synaptic plasticity and fear conditioning (23,24). A naturally occurring for polymorphism with two variants, for R (rover) and for s (sitter), is maintained in wild populations of D. melanogaster.…”