Beldjoud Hassiba, Barsegyan Areg, Roozendaal Benno
Department of Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Netherlands ; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Nijmegen, Netherlands.
Front Behav Neurosci. 2015 Apr 28;9:108. doi: 10.3389/fnbeh.2015.00108. eCollection 2015.
It is well established that arousal-induced memory enhancement requires noradrenergic activation of the basolateral complex of the amygdala (BLA) and modulatory influences on information storage processes in its many target regions. While this concept is well accepted, the molecular basis of such BLA effects on neural plasticity changes within other brain regions remains to be elucidated. The present study investigated whether noradrenergic activation of the BLA after object recognition training induces chromatin remodeling through histone post-translational modifications in the insular cortex (IC), a brain region that is importantly involved in object recognition memory. Male Sprague-Dawley rats were trained on an object recognition task, followed immediately by bilateral microinfusions of norepinephrine (1.0 μg) or saline administered into the BLA. Saline-treated control rats exhibited poor 24-h retention, whereas norepinephrine treatment induced robust 24-h object recognition memory. Most importantly, this memory-enhancing dose of norepinephrine induced a global reduction in the acetylation levels of histone H3 at lysine 14, H2B and H4 in the IC 1 h later, whereas it had no effect on the phosphorylation of histone H3 at serine 10 or tri-methylation of histone H3 at lysine 27. Norepinephrine administered into the BLA of non-trained control rats did not induce any changes in the histone marks investigated in this study. These findings indicate that noradrenergic activation of the BLA induces training-specific effects on chromatin remodeling mechanisms, and presumably gene transcription, in its target regions, which may contribute to the understanding of the molecular mechanisms of stress and emotional arousal effects on memory consolidation.
众所周知，唤醒诱导的记忆增强需要杏仁核基底外侧复合体（BLA）的去甲肾上腺素能激活以及对其许多靶区域信息存储过程的调节影响。虽然这一概念已被广泛接受，但BLA对其他脑区神经可塑性变化的分子基础仍有待阐明。本研究调查了在物体识别训练后，BLA的去甲肾上腺素能激活是否通过岛叶皮质（IC）中的组蛋白翻译后修饰诱导染色质重塑，岛叶皮质是一个在物体识别记忆中起重要作用的脑区。雄性Sprague-Dawley大鼠接受物体识别任务训练，随后立即向BLA双侧微量注射去甲肾上腺素（1.0μg）或生理盐水。生理盐水处理的对照大鼠24小时记忆保持较差，而去甲肾上腺素处理诱导了强大的24小时物体识别记忆。最重要的是，这种增强记忆剂量的去甲肾上腺素在1小时后导致IC中赖氨酸14处组蛋白H3、H2B和H4的乙酰化水平整体降低，而对丝氨酸10处组蛋白H3的磷酸化或赖氨酸27处组蛋白H3的三甲基化没有影响。向未训练的对照大鼠的BLA注射去甲肾上腺素不会诱导本研究中所研究的组蛋白标记的任何变化。这些发现表明，BLA的去甲肾上腺素能激活在其靶区域诱导对染色质重塑机制以及推测的基因转录的训练特异性效应，这可能有助于理解应激和情绪唤醒对记忆巩固影响的分子机制。
