Manipulation of hippocampal CA3 firing via luminopsins modulates spatial and episodic short-term memory, especially working memory, but not long-term memory

Manipulation of hippocampal CA3 firing via luminopsins modulates spatial and episodic short-term memory, especially working memory, but not long-term memory
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通过发光蛋白操纵海马 CA3 放电可调节空间和情景短期记忆,尤其是工作记忆,但不能调节长期记忆

DOI:
10.1016/j.nlm.2018.09.009
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发表时间:
2018-09
影响因子:
2.7
通讯作者:
Qing Hong
Qing Hong
中科院分区:
心理学4区
文献类型:
--
作者:
Song Da;Yang Qinghu;Lang Yiran;Wen Zhaosen;Xie Zhen;Zheng Da;Yan Tianyi;Deng Yujun;Nakanishi Hiroshi;Quan Zhenzhen;Qing Hong

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海马区的CA3亚区对于联想记忆的快速编码、存储和提取非常重要。海马CA3区的损伤和药物抑制表明,它对不同的记忆是必不可少的。然而,CA3在不同时间尺度(即短期和长期)中如何在没有永久性损伤的情况下在空间和情景记忆中发挥作用还没有得到系统的研究。利用视蛋白的化学发生途径,本研究使用发光素,荧光素酶和光遗传元件的融合蛋白,在一系列空间和时间尺度上的记忆任务中操纵CA3中的神经元活动。在本研究中,我们发现CA3神经元的兴奋或抑制对长时空间记忆和情景记忆没有显著影响,但对空间工作记忆、空间短时记忆和情景短时记忆有显著影响。此外,刺激CA3神经元改变了NR2A的表达水平。脑内注射受体抑制剂进一步证实了NR2A对空间工作记忆至关重要,这与发光素的实验结果是一致的。这些发现表明,CA3在短时间内对空间记忆和情景记忆具有特定的作用。
The CA3 subregion of the hippocampus is important for rapid encoding, storage and retrieval of associative memories. Lesions and pharmacological inhibitions of hippocampal CA3 suggest that it is essential for different memories. However, how CA3 functions in spatial and episodic memory in different time scales (i.e. short-term versus long term) without permanent lesions has not been systematically investigated yet. Taking advantage of the chemogenetic access to opsins, this study used luminopsins, fusion proteins of luciferase and optogenetic elements, to manipulate neuronal activity in CA3 during memory tasks over a range of spatial and temporal scales. In this study, we found that excitation or inhibition of CA3 neurons had no significant effects on long-term spatial or episodic memory, but had remarkable effects on spatial working memory, spatial short-term memory as well as episodic short-term memory. In addition, stimulation of CA3 neurons altered the expression levels of NR2A. Intracerebral injection of receptor inhibitors further confirmed that NR2A is crucial to spatial working memory, which is consistent with the luminopsins experiments. These findings indicate that CA3 maintains a specific role on spatial and episodic memory over a short period of time.
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