Neurobiology of Decision Making, Paris-Saclay Institute of Neuroscience (NeuroPSI), CNRS, University Paris-Saclay, Gif-sur-Yvett, France.
University of Turku, Turku, Finland.
PLoS One. 2022 Aug 4;17(8):e0272141. doi: 10.1371/journal.pone.0272141. eCollection 2022.
The cholinergic system is an important modulator of brain processes. It contributes to the regulation of several cognitive functions and emotional states, hence altering behaviors. Previous works showed that cholinergic (nicotinic) receptors of the prefrontal cortex are needed for adapted social behaviors. However, these data were obtained in mutant mice that also present alterations of several neurotransmitter systems, in addition to the cholinergic system. ChAT-IRES-Cre mice, that express the Cre recombinase specifically in cholinergic neurons, are useful tools to investigate the role of the cholinergic circuits in behavior. However, their own behavioral phenotype has not yet been fully characterized, in particular social behavior. In addition, the consequences of aging on the cholinergic system of ChAT-IRES-Cre mice has never been studied, despite the fact that aging is known to compromise the cholinergic system efficiency. The aim of the current study was thus to characterize the social phenotype of ChAT-IRES-Cre mice both at young (2-3 months) and middle (10-11 months) ages. Our results reveal an alteration of the cholinergic system, evidenced by a decrease of ChAT, CHT and VAChT gene expression in the striatum of the mice, that was accompanied by mild social disturbances and a tendency towards anxiety. Aging decreased social dominance, without being amplified by the cholinergic alterations. Altogether, this study shows that ChAT-IRES-Cre mice are useful models for studying the cholinergic system's role in social behavior using appropriate modulating technics (optogenetic or DREADD).
胆碱能系统是大脑过程的重要调节剂。它有助于调节几种认知功能和情绪状态，从而改变行为。以前的工作表明，前额叶皮层的胆碱能（烟碱型）受体对于适应性社会行为是必需的。然而，这些数据是在突变小鼠中获得的，这些小鼠除了胆碱能系统外，还存在几种神经递质系统的改变。在胆碱能神经元中特异性表达 Cre 重组酶的 ChAT-IRES-Cre 小鼠是研究胆碱能回路在行为中的作用的有用工具。然而，它们自己的行为表型尚未得到充分表征，特别是社会行为。此外，尽管众所周知衰老会影响胆碱能系统的效率，但衰老对 ChAT-IRES-Cre 小鼠的胆碱能系统的影响从未被研究过。本研究的目的是在年轻（2-3 个月）和中年（10-11 个月）两个年龄段描述 ChAT-IRES-Cre 小鼠的社会表型。我们的结果揭示了胆碱能系统的改变，表现为纹状体中 ChAT、CHT 和 VAChT 基因表达的减少，这伴随着轻微的社交障碍和焦虑倾向。衰老降低了社会优势，但没有被胆碱能改变放大。总之，这项研究表明，ChAT-IRES-Cre 小鼠是使用适当的调节技术（光遗传学或 DREADD）研究胆碱能系统在社会行为中的作用的有用模型。
