PDF(Pubmed)
Abstract：
UNASSIGNED: Cumulative 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.
UNASSIGNED: In 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.
UNASSIGNED: We 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.
UNASSIGNED: These findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.
UNASSIGNED: In 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.
UNASSIGNED: We 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.
UNASSIGNED: These findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.
摘要：
■累积证据表明，感觉皮质与基底外侧杏仁核（BLA）防御回路相互作用，以调解威胁条件，记忆检索,和灭绝学习。嗅梨状皮层（PC）已被认为是嗅觉联想记忆的关键部位。最近,我们已经证明，PC中N-甲基-D-天冬氨酸受体（NMDAR）依赖性可塑性是嗅觉威胁灭绝的关键基础。嗅觉威胁消失的衰老相关损害与PC中NMDAR的功能低下有关。
■在这项研究中，我们使用免疫组织化学研究了BLA和PC中神经元cfos和表观遗传标记的激活，在大鼠的嗅觉威胁条件和灭绝学习之后。
■我们发现后PC（pPC）和BLA之间的cFos激活高度相关。cFos与成年和老年大鼠pPC的行为冻结程度相关，在BLA中只有成年大鼠。DNA甲基化5mC和组蛋白乙酰化H3K9/K14ac的标记，H3K27ac,和H4ac展示了独特的训练-，区域-,和年龄相关的激活模式。发现成年大鼠中BLA和pPC之间的表观遗传标记的强相关性是一般特征。相反，老年大鼠仅表现出两种结构之间H3乙酰化的相关性。组蛋白乙酰化随衰老而变化，在基础条件和威胁条件下，老年大脑中H3K9/K14ac的减少和H4ac的增加揭示了这一点。
■这些发现强调了PC和BLA在嗅觉联想记忆存储和灭绝中的协调作用，对理解衰老相关的认知能力下降具有重要意义。
■在这项研究中，我们使用免疫组织化学研究了BLA和PC中神经元cfos和表观遗传标记的激活，在大鼠的嗅觉威胁条件和灭绝学习之后。
■我们发现后PC（pPC）和BLA之间的cFos激活高度相关。cFos与成年和老年大鼠pPC的行为冻结程度相关，在BLA中只有成年大鼠。DNA甲基化5mC和组蛋白乙酰化H3K9/K14ac的标记，H3K27ac,和H4ac展示了独特的训练-，区域-,和年龄相关的激活模式。发现成年大鼠中BLA和pPC之间的表观遗传标记的强相关性是一般特征。相反，老年大鼠仅表现出两种结构之间H3乙酰化的相关性。组蛋白乙酰化随衰老而变化，在基础条件和威胁条件下，老年大脑中H3K9/K14ac的减少和H4ac的增加揭示了这一点。
■这些发现强调了PC和BLA在嗅觉联想记忆存储和灭绝中的协调作用，对理解衰老相关的认知能力下降具有重要意义。
