美国耶鲁大学医学院Jessica A. Cardin团队近期取得重要工作进展，他们研究提出了胆碱能和新皮质活动的时空异质性协调的观点。相关研究成果2022年11月28日在线发表于《自然—神经科学》杂志上。

据介绍，动物行为状态的变化与大脑活动和认知能力的波动有关。在新皮质中，状态依赖性回路动力学可能反映神经调节影响，如乙酰胆碱（ACh）。尽管早期文献表明ACh对皮质功能具有广泛、均匀的控制，但最近的证据表明胆碱能信号可能存在解剖学和功能上的分离。此外，尚不清楚不同行为标志物定义的状态是否反映了异质的胆碱能和皮层网络活动。

研究人员通过同时对清醒小鼠大脑皮层的ACh和钙进行双色介观成像，以研究它们与行为变量的关系。他们发现，根据不同的运动行为分类，较高的觉醒与胆碱能调节的时空动态模式和增强的大规模网络相关性有关。

总之，这一发现表明ACh提供了一种高度动态和空间异质性信号，将行为的波动与皮层网络的功能重组联系起来。

附：英文原文

Title: Spatiotemporally heterogeneous coordination of cholinergic and neocortical activity

Author: Lohani, Sweyta, Moberly, Andrew H., Benisty, Hadas, Landa, Boris, Jing, Miao, Li, Yulong, Higley, Michael J., Cardin, Jessica A.

Issue&Volume: 2022-11-28

Abstract: Variation in an animal’s behavioral state is linked to fluctuations in brain activity and cognitive ability. In the neocortex, state-dependent circuit dynamics may reflect neuromodulatory influences such as that of acetylcholine (ACh). Although early literature suggested that ACh exerts broad, homogeneous control over cortical function, recent evidence indicates potential anatomical and functional segregation of cholinergic signaling. In addition, it is unclear whether states as defined by different behavioral markers reflect heterogeneous cholinergic and cortical network activity. Here, we perform simultaneous, dual-color mesoscopic imaging of both ACh and calcium across the neocortex of awake mice to investigate their relationships with behavioral variables. We find that higher arousal, categorized by different motor behaviors, is associated with spatiotemporally dynamic patterns of cholinergic modulation and enhanced large-scale network correlations. Overall, our findings demonstrate that ACh provides a highly dynamic and spatially heterogeneous signal that links fluctuations in behavior to functional reorganization of cortical networks.

DOI: 10.1038/s41593-022-01202-6

Source: https://www.nature.com/articles/s41593-022-01202-6