Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
Department of Neurohumoral Regulations, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Sci Rep. 2018 Oct 19;8(1):15547. doi: 10.1038/s41598-018-33637-y.
Animals create implicit memories of the time of day that significant events occur then anticipate the recurrence of those conditions at the same time on subsequent days. We tested the hypothesis that implicit time memory for daily encounters relies on the setting of the canonical circadian clockwork in brain areas involved in the formation or expression of context memories. We conditioned mice to avoid locations paired with a mild foot shock at one of two Zeitgeber times set 8 hours apart. Place avoidance was exhibited only when testing time matched the prior training time. The suprachiasmatic nucleus, dorsal striatum, nucleus accumbens, cingulate cortex, hippocampal complex, and amygdala were assessed for clock gene expression. Baseline phase dependent differences in clock gene expression were found in most tissues. Evidence for conditioned resetting of a molecular circadian oscillation was found only in the striatum (dorsal striatum and nucleus accumbens shell), and specifically for Per2 expression. There was no evidence of glucocorticoid stress response in any tissue. The results are consistent with a model where temporal conditioning promotes a selective Per2 response in dopamine-targeted brain regions responsible for sensorimotor integration, without resetting the entire circadian clockwork.
动物会创建关于重要事件发生时间的内隐记忆,然后预测这些条件在随后的日子里会在同一时间再次发生。我们假设,对于日常遭遇的内隐时间记忆依赖于大脑中涉及形成或表达情境记忆的区域中的生物钟的设置。我们使老鼠习惯于在两个时间(相隔 8 小时)中的一个时间回避与轻度足部电击配对的位置。只有在测试时间与之前的训练时间匹配时,才会表现出回避行为。评估了视交叉上核、背侧纹状体、伏隔核、扣带回皮层、海马复合体和杏仁核中的时钟基因表达。在大多数组织中都发现了生物钟基因表达的基线相位依赖性差异。只有在纹状体(背侧纹状体和伏隔核壳)中发现了条件重置的分子生物钟振荡的证据,特别是对于 Per2 表达。在任何组织中都没有发现糖皮质激素应激反应的证据。这些结果与一个模型一致,即时间条件作用促进了负责感觉运动整合的多巴胺靶向脑区中 Per2 的选择性反应,而不会重置整个生物钟。