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基于神经元活动化学遗传调控视角下的脑连接性

Connectivity of the Brain in the Light of Chemogenetic Modulation of Neuronal Activity.

作者信息

Dygalo N N

机构信息

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IC&G SB RAS), Novosibirsk, 630090 Russian Federation.

出版信息

Acta Naturae. 2023 Apr-Jun;15(2):4-13. doi: 10.32607/actanaturae.11895.

DOI:10.32607/actanaturae.11895
PMID:37538804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10395778/
Abstract

Connectivity is the coordinated activity of the neuronal networks responsible for brain functions; it is detected based on functional magnetic resonance imaging signals that depend on the oxygen level in the blood (blood oxygen level-dependent (BOLD) signals) supplying the brain. The BOLD signal is only indirectly related to the underlying neuronal activity; therefore, it remains an open question whether connectivity and changes in it are only manifestations of normal and pathological states of the brain or they are, to some extent, the causes of these states. The creation of chemogenetic receptors activated by synthetic drugs (designer receptors exclusively activated by designer drugs, DREADDs), which, depending on the receptor type, either facilitate or, on the contrary, inhibit the neuronal response to received physiological stimuli, makes it possible to assess brain connectivity in the light of controlled neuronal activity. Evidence suggests that connectivity is based on neuronal activity and is a manifestation of connections between brain regions that integrate sensory, cognitive, and motor functions. Chemogenetic modulation of the activity of various groups and types of neurons changes the connectivity of the brain and its complex functions. Chemogenetics can be useful in reconfiguring the pathological mechanisms of nervous and mental diseases. The initiated integration, based on the whole-brain connectome from molecular-cellular, neuronal, and synaptic processes to higher nervous activity and behavior, has the potential to significantly increase the fundamental and applied value of this branch of neuroscience.

摘要

连通性是负责大脑功能的神经网络的协同活动;它是根据功能磁共振成像信号检测到的,这些信号取决于供应大脑的血液中的氧水平(血氧水平依赖(BOLD)信号)。BOLD信号仅与潜在的神经元活动间接相关;因此,连通性及其变化仅仅是大脑正常和病理状态的表现,还是在某种程度上是这些状态的原因,这仍然是一个悬而未决的问题。合成药物激活的化学遗传受体(仅由设计药物激活的设计受体,DREADDs)的产生,根据受体类型,要么促进要么相反抑制神经元对所接收生理刺激的反应,这使得根据受控的神经元活动来评估大脑连通性成为可能。有证据表明,连通性基于神经元活动,是整合感觉、认知和运动功能的脑区之间连接的一种表现。对各种神经元群体和类型的活动进行化学遗传调节会改变大脑的连通性及其复杂功能。化学遗传学在重新配置神经和精神疾病的病理机制方面可能有用。基于从分子细胞、神经元和突触过程到高级神经活动和行为的全脑连接组所启动的整合,有可能显著提高神经科学这一分支的基础和应用价值。

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本文引用的文献

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Increased fMRI connectivity upon chemogenetic inhibition of the mouse prefrontal cortex.化学遗传抑制小鼠前额叶皮层后 fMRI 连接增加。
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