Molecular mechanisms underlying cholinergic signaling in developing neurons

发育中神经元胆碱能信号传导的分子机制

基本信息

批准号：
436190-2013
负责人：
Bailey, Craig
金额：
$ 2.33万
依托单位：
University of Guelph
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2018
资助国家：
加拿大
起止时间：
2018-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=644483
关键词：
Molecular mechanisms underlying cholinergic signaling

项目摘要

The brain uses a chemical messenger called acetylcholine to fine-tune its own performance. One prominent site of action for acetylcholine in the mature brain is the prefrontal cortex, where it plays a critical role in regulating higher-order cognitive functions such as learning, memory and attention. Acetylcholine likely also influences the development of the prefrontal cortex, as it is first produced while the brain is still developing, and its effects on neurons within the prefrontal cortex are greater at a time when this brain region enters late stages of maturation compared with when it is fully matured. This heightened effectiveness places acetylcholine in a prime position to influence the normal maturation of neurons within the prefrontal cortex, thus imparting a long-term influence on cognitive function. However, many questions remain unanswered because the reasoning behind this heightened effectiveness is not known. The proposed research program aims to answer these questions by determining the mechanisms underlying the heightened acetylcholine signaling seen during prefrontal cortex development, and in turn, what influence this acetylcholine signaling has on the maturation of neurons within the prefrontal cortex. Discoveries made by this research program will contribute to our fundamental understanding of cognitive systems development and will provide a foundation from which to study how the development of these systems may be altered by external factors such as exposure to a stressful environment.

大脑使用称为乙酰胆碱的化学信使来微调自己的性能。乙酰胆碱在成熟大脑中的一个突出的作用部位是前额叶皮层，它在调节高阶认知功能（例如学习，记忆和注意力）中起着至关重要的作用。乙酰胆碱可能还会影响前额叶皮层的发育，因为它是在大脑仍在发育的同时首次产生的，并且在该大脑区域进入成熟的晚期与完全成熟时的成熟阶段时，其对前额叶皮层内神经元的影响更大。这种提高的有效性使乙酰胆碱处于主要位置，以影响前额叶皮层内神经元正常成熟，从而对认知功能产生长期影响。但是，许多问题仍然没有得到答复，因为尚不清楚这种提高有效性背后的推理。拟议的研究计划旨在通过确定前额叶皮层发育过程中看到的乙酰胆碱信号增强的基础机制来回答这些问题，进而影响这种乙酰胆碱信号传导对前额叶皮质内神经元成熟的影响。该研究计划提出的发现将有助于我们对认知系统发展的基本理解，并将为研究这些系统的开发如何通过外部因素（例如暴露于压力性环境）来改变这些基础。