Molecularly defined and functionally distinct cholinergic subnetworks
Molecularly defined and functionally distinct cholinergic subnetworks
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分子定义且功能独特的胆碱能子网络
DOI：
10.1016/j.neuron.2022.08.025
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发表时间：
2022-11-16
期刊：
影响因子：
16.2
通讯作者：
Lu, Youming
中科院分区：
文献类型：
--
作者：
Li, Xinyan;Yu, Hongyan;Lu, Youming
内侧隔（MS）中的胆碱能神经元构成前脑胆碱能输入的主要来源，并调节多种功能，包括感觉处理、记忆和注意。迄今为止，大多数研究都将胆碱能神经元作为一个单一的群体，因此，其功能多样性的组织原则仍然未知。在这里，我们确定了两个子集（D28 K（+）与D28 K（-））的胆碱能神经元，在小鼠，食蟹猴，和人类的地形隔离。这些胆碱能亚群具有独特的电生理特征，表达相互排斥的标记基因（kcnh 1和aifm 3与cacna 1h和gga 3），并与海马中生理学上不同的神经元类别建立差异连接，形成两个结构上定义和功能上不同的回路。对这些回路的功能获得和丧失的研究揭示了它们在调节焦虑样行为和空间记忆中的不同作用。这些结果为胆碱能神经元如何促进其不同的行为功能提供了一个基于分子和电路的理论。
Cholinergic neurons in the medial septum (MS) constitute a major source of cholinergic input to the forebrain and modulate diverse functions, including sensory processing, memory, and attention. Most studies to date have treated cholinergic neurons as a single population; as such, the organizational principles underling their functional diversity remain unknown. Here, we identified two subsets (D28K(+) versus D28K(-)) of cholinergic neurons that are topographically segregated in mice, Macaca fascicularis, and humans. These cholinergic subpopulations possess unique electrophysiological signatures, express mutually exclusive marker genes (kcnh1 and aifm3 versus cacna1h and gga3), and make differential connections with physiologically distinct neuronal classes in the hippocampus to form two structurally defined and functionally distinct circuits. Gain- and loss-of-function studies on these circuits revealed their differential roles in modulation of anxiety-like behavior and spatial memory. These results provide a molecular and circuitry-based theory for how cholinergic neurons contribute to their diverse behavioral functions.