Correlational patterns of neuronal activation and epigenetic marks in the basolateral amygdala and piriform cortex following olfactory threat conditioning and extinction in rats

Abstract

IntroductionCumulative evidence suggests that sensory cortices interact with the basolateral amygdala (BLA) defense circuitry to mediate threat conditioning, memory retrieval, and extinction learning. The olfactory piriform cortex (PC) has been posited as a critical site for olfactory associative memory. Recently, we have shown that N-methyl-D-aspartate receptor (NMDAR)-dependent plasticity in the PC critically underpins olfactory threat extinction. Aging-associated impairment of olfactory threat extinction is related to the hypofunction of NMDARs in the PC.MethodsIn this study, we investigated activation of neuronal cFos and epigenetic marks in the BLA and PC using immunohistochemistry, following olfactory threat conditioning and extinction learning in rats.ResultsWe found highly correlated cFos activation between the posterior PC (pPC) and BLA. cFos was correlated with the degree of behavioral freezing in the pPC in both adult and aged rats, and in the BLA only in adult rats. Markers of DNA methylation 5 mC and histone acetylation H3K9/K14ac, H3K27ac, and H4ac exhibited distinct training-, region-, and age-dependent patterns of activation. Strong correlations of epigenetic marks between the BLA and pPC in adult rats were found to be a general feature. Conversely, aged rats only exhibited correlations of H3 acetylations between the two structures. Histone acetylation varied as a function of aging, revealed by a reduction of H3K9/K14ac and an increase of H4ac in aged brains at basal condition and following threat conditioning.DiscussionThese findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.

The role of Foxo3a in neuron-mediated cognitive impairment

“…Persistent COI seriously affects the recovery of patients’ ability to live autonomously. The development of COI is closely associated with damage in specific brain regions such as the hippocampus ( Lisman et al, 2017 ), dorsolateral prefrontal cortex ( Joyce et al, 2024 ), lateral amygdala ( Qin et al, 2024 ), and pyriform cortex ( Qin et al, 2024 ). In the field of brain rehabilitation therapy in recent years, the restoration of cognitive function has garnered significant recognition as a fundamental aspect of recovering brain functionality.…”