Regulation of Cognitive Processing by Hippocampal Cholinergic Tone
Regulation of Cognitive Processing by Hippocampal Cholinergic Tone
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DOI：
10.1093/cercor/bhv349
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发表时间：
2017-02-01
期刊：
影响因子：
3.7
通讯作者：
Prado, Vania F.
中科院分区：
文献类型：
--
作者：
Al-Onaizi, Mohammed A.;Parfitt, Gustavo M.;Prado, Vania F.
胆碱能功能障碍与多种神经退行性疾病和神经精神疾病的认知异常有关。在这里，我们测试了基因改造小鼠中胆碱能张力如何调节信息处理，该小鼠靶向囊泡乙酰胆碱转运蛋白（VAChT），这是一种乙酰胆碱释放所需的蛋白质。我们测量了体内 Schaffer 侧支 CA1 突触的长期增强，并通过使用鼠标触摸屏版本的配对关联学习任务 (PAL) 评估了信息处理。小鼠 PAL 任务中信息的获取与海马 VAChT 水平相关，表明胆碱能张力的关键作用。因此，体内海马的突触可塑性因海马胆碱能信号传导的减少而受到干扰，但并未完全消除。前脑胆碱能信号传导中断也会影响工作记忆，这一结果是通过选择性降低海马体中的 VAChT 来重现的。相比之下，空间记忆相对保留，而逆转空间记忆对海马胆碱能信号减弱敏感。这项工作提供了突触分泌的乙酰胆碱如何影响不同行为的精细路线图，并表明不同形式的认知处理可能通过胆碱能活动以不同的方式进行调节。
Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric diseases. Here we tested how information processing is regulated by cholinergic tone in genetically modified mice targeting the vesicular acetylcholine transporter (VAChT), a protein required for acetylcholine release. We measured long-term potentiation of Schaffer collateral-CA1 synapses in vivo and assessed information processing by using a mouse touchscreen version of paired associates learning task (PAL). Acquisition of information in the mouse PAL task correlated to levels of hippocampal VAChT, suggesting a critical role for cholinergic tone. Accordingly, synaptic plasticity in the hippocampus in vivo was disturbed, but not completely abolished, by decreased hippocampal cholinergic signaling. Disrupted forebrain cholinergic signaling also affected working memory, a result reproduced by selectively decreasing VAChT in the hippocampus. In contrast, spatial memory was relatively preserved, whereas reversal spatial memory was sensitive to decreased hippocampal cholinergic signaling. This work provides a refined roadmap of how synaptically secreted acetylcholine influences distinct behaviors and suggests that distinct forms of cognitive processing may be regulated in different ways by cholinergic activity.