The circadian clock gene Per1 modulates context fear memory formation within the retrosplenial cortex in a sex-specific manner.
The circadian clock gene Per1 modulates context fear memory formation within the retrosplenial cortex in a sex-specific manner.
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DOI：
10.1016/j.nlm.2021.107535
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发表时间：
2021-11
影响因子：
2.7
通讯作者：
Kwapis JL
中科院分区：
文献类型：
--
作者：
Urban MW;Lo C;Bodinayake KK;Brunswick CA;Murakami S;Heimann AC;Kwapis JL
背景记忆的形成是一个复杂的过程，需要在包括背侧海马和压后皮质在内的许多脑亚区进行转录。昼夜节律基因Period 1（Per 1）是记忆形成所必需的一个关键基因，除了在视交叉上核（SCN）内调节昼夜时钟的作用外，它还在背侧海马中发挥调节空间记忆的作用。我们最近发现，Per 1在背侧海马表达的改变可以调节空间记忆的形成，减少海马Per 1损害记忆和Per 1的过度表达改善空间记忆中的年龄相关的障碍。Per 1是否在其他与记忆相关的大脑区域中也有类似的功能，目前尚不清楚。在这里，为了测试Per 1是否是一种调节大脑记忆的一般机制，我们测试了Per 1在压后皮质（RSC）中的作用，这是一个形成背景记忆所必需的大脑区域。首先，我们证明了背景恐惧条件反射驱动前RSC内Per 1 mRNA表达的短暂增加，在训练后60 m达到峰值。接下来，使用HSV-CRISPRi介导的Per 1敲低，我们表明在上下文恐惧获得之前减少前RSC内的Per 1会损害雄性和雌性小鼠的记忆。相比之下，在背景恐惧获得之前用HSV-CRISPRa或HSV-Per 1过表达Per 1会导致性别特异性记忆障碍;男性显示背景恐惧记忆受损，而女性不受Per 1过表达的影响。最后，由于Per 1水平在白天/夜晚周期中有节奏地振荡，我们测试了Per 1过表达可能对记忆产生不同影响的可能性，这取决于一天中的时间。与我们在白天观察到的记忆障碍相反，Per 1过表达对雄性或雌性小鼠在夜间的背景恐惧记忆没有影响。总之，我们的研究结果表明，Per 1调节记忆的前压后皮质除了其记录的作用，在背海马内的记忆调节，虽然这种作用可能会有所不同的男性和女性。
Context memory formation is a complex process which requires transcription in many subregions of the brain including the dorsal hippocampus and retrosplenial cortex. One critical gene necessary for memory formation is the circadian gene Period1 (Per1), which has been shown to function in the dorsal hippocampus to modulate spatial memory in addition to its well-documented role in regulating the diurnal clock within the suprachiasmatic nucleus (SCN). We recently found that alterations in Per1 expression in the dorsal hippocampus can modulate spatial memory formation, with reduced hippocampal Per1 impairing memory and overexpression of Per1 ameliorating age-related impairments in spatial memory. Whether Per1 similarly functions within other memory-relevant brain regions is currently unknown. Here, to test whether Per1 is a general mechanism that modulates memory across the brain, we tested the role of Per1 in the retrosplenial cortex (RSC), a brain region necessary for context memory formation. First, we demonstrate that context fear conditioning drives a transient increase in Per1 mRNA expression within the anterior RSC that peaks 60m after training. Next, using HSV-CRISPRi-mediated knockdown of Per1, we show that reducing Per1 within the anterior RSC before context fear acquisition impairs memory in both male and female mice. In contrast, overexpressing Per1 with either HSV-CRISPRa or HSV-Per1 before context fear acquisition drives a sex-specific memory impairment; males show impaired context fear memory whereas females are not affected by Per1 overexpression. Finally, as Per1 levels are known to rhythmically oscillate across the day/night cycle, we tested the possibility that Per1 overexpression might have different effects on memory depending on the time of day. In contrast to the impairment in memory we observed during the daytime, Per1 overexpression has no effect on context fear memory during the night in either male or female mice. Together, our results indicate that Per1 modulates memory in the anterior retrosplenial cortex in addition to its documented role in regulating memory within the dorsal hippocampus, although this role may differ between males and females.
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影响因子：
4.8
作者：
Albrecht U
通讯作者：
Albrecht U
影响因子：
--
作者：
Marcheva, Biliana;Ramsey, Kathryn M;Peek, Clara B;Affinati, Alison;Maury, Eleonore;Bass, Joseph
通讯作者：
Bass, Joseph
影响因子：
3.7
作者：
Bohacek, Johannes;Manuella, Francesca;Mansuy, Isabelle M.
通讯作者：
Mansuy, Isabelle M.
影响因子：
2.7
作者：
Lehner, Malgorzata;Wislowska-Stanek, Aleksandra;Plaznik, Adam
通讯作者：
Plaznik, Adam
DOI：
10.1523/jneurosci.2107-11.2011
发表时间：
2011-08-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Corcoran KA;Donnan MD;Tronson NC;Guzmán YF;Gao C;Jovasevic V;Guedea AL;Radulovic J
通讯作者：
Radulovic J