A hypothalamic novelty signal modulates hippocampal memory
A hypothalamic novelty signal modulates hippocampal memory
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DOI：
10.1038/s41586-020-2771-1
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发表时间：
2020-09-30
期刊：
影响因子：
64.8
通讯作者：
McHugh, Thomas J.
中科院分区：
文献类型：
--
作者：
Chen, Shuo;He, Linmeng;McHugh, Thomas J.
识别与先前经验不一致的信息的能力对于生存至关重要。新奇信号因此在哺乳动物大脑中进化，以增强注意力，感知和记忆（1，2）。尽管腹侧被盖区（3，4）和蓝斑（5）等区域在广泛的新奇信号传递中的重要性已经得到了充分的证实，但这些弥散性单胺能递质尚未被证明能够传递有关驱动它们的刺激类型的特定信息。不同类型的新奇事物，如背景新奇事物和社会新奇事物，是否在大脑中以不同的方式处理和路由尚不清楚。在这里，我们将乳头体上核（SuM）确定为下丘脑中的新奇枢纽（6）。该SuM区域是独特的，因为它不仅广泛地响应新的刺激，但也隔离和选择性地路由不同类型的信息到离散的皮层目标-齿状回和CA 2领域的campus-for调制的记忆处理。使用一种新的转基因小鼠系，SuM-Cre，我们发现，SuM神经元项目的齿状回被激活的上下文新奇，而SuM-CA 2电路优先激活的新的社会遭遇。基于电路的操作表明，在这些预测不同的新奇通道修改海马上下文或社会记忆。新奇信号的这种内容特异性路由代表了一种以前未知的机制，它使下丘脑能够灵活地调节认知的选择成分，下丘脑的乳头体上核（suprammillary nucleus）就像一个新奇中枢，它选择性地将不同类型的新奇信号引导到海马体的不同子区域，并灵活地调节记忆的编码。
The ability to recognize information that is incongruous with previous experience is critical for survival. Novelty signals have therefore evolved in the mammalian brain to enhance attention, perception and memory(1,2). Although the importance of regions such as the ventral tegmental area(3,4)and locus coeruleus(5)in broadly signalling novelty is well-established, these diffuse monoaminergic transmitters have yet to be shown to convey specific information on the type of stimuli that drive them. Whether distinct types of novelty, such as contextual and social novelty, are differently processed and routed in the brain is unknown. Here we identify the supramammillary nucleus (SuM) as a novelty hub in the hypothalamus(6). The SuM region is unique in that it not only responds broadly to novel stimuli, but also segregates and selectively routes different types of information to discrete cortical targets-the dentate gyrus and CA2 fields of the hippocampus-for the modulation of mnemonic processing. Using a new transgenic mouse line, SuM-Cre, we found that SuM neurons that project to the dentate gyrus are activated by contextual novelty, whereas the SuM-CA2 circuit is preferentially activated by novel social encounters. Circuit-based manipulation showed that divergent novelty channelling in these projections modifies hippocampal contextual or social memory. This content-specific routing of novelty signals represents a previously unknown mechanism that enables the hypothalamus to flexibly modulate select components of cognition.The supramammillary nucleus in the hypothalamus acts as a novelty hub that selectively directs different types of novelty signals to different subregions of the hippocampus and flexibly modulates the encoding of memory.