前额外内神经元的海马输入驱动的可塑性揭示了空间工作记忆受损的电路基础
Shana E Silverstein1, Thomas T Clarity1, Meena S Deshpande1
1Integrative Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
bioRxiv : the preprint server for biology
|August 8, 2025
概括
动态大脑连接是空间工作记忆 (SWM) 的关键. 这项研究表明,中枢前额叶皮层中神经细胞的特定可塑性如何影响SWM,为记忆障碍提供了洞察力.
科学领域:
- 神经科学是一个神经科学.
- 认知神经科学 认知神经科学
- 细胞神经科学 细胞神经科学
背景情况:
- 腹部海马体 (vHPC) 和中部前额叶皮层 (mPFC) 之间的动态功能连接对于空间工作记忆 (SWM) 是至关重要的.
- 影响SWM的vHPC投射和mPFC内部神经元之间的相互作用和可塑性的确切性质尚不清楚.
研究的目的:
- 为了研究mPFC内部神经元对vHPC输入刺激的细胞类型特异性反应概况和可塑性.
- 阐明SWM背后的电路机制以及vHPC-mPFC连接中的可塑性如何影响SWM性能.
- 检查异常内部神经元活动在22q11.2删除综合征的小鼠模型,与SWM缺陷相关的条件.
主要方法:
- 将vHPC输入到mPFC的组合in vivo光学刺激与小鼠不同的mPFC内部神经元群体的记录.
- 利用全细胞电生理学和计算建模来理解突触可塑性机制.
- 评估SWM任务性能和与行为结果相关的神经活动.
主要成果:
- 重复的vHPC刺激导致血管活性肠 (VIP) 表达性内神经元的持续抑制和体静止素表达性内神经元的强化.
- 将单突触vHPC输入到VIP内部神经元的削弱被确定为这些不同的效应的可能原因.
- 之前的vHPC输入刺激导致SWM任务延迟时期的VIP内部神经元活动升高,与较差的性能相关.
- 模拟22q11.2删除综合征的小鼠表现出类似的异常VIP内部神经元活动和减少mPFCVIP内部神经元的vHPC向.
结论:
- 在支持认知的电路中揭示了新的细胞类型特定可塑性.
- 证明了对VIP内部神经元输入的重量调整可以导致工作记忆功能障碍.
- 突出了vHPC-mPFC电路可塑性在SWM中的作用及其与精神分裂症等神经发育障碍的潜在相关性.
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