Molecular mechanisms underlying cholinergic signaling in developing neurons

大脑使用一种叫做乙酰胆碱的化学信使来微调自己的表现。乙酰胆碱在成熟大脑中的一个重要作用部位是前额叶皮层，在那里它在调节高级认知功能（如学习，记忆和注意力）中起着关键作用。乙酰胆碱可能也会影响前额叶皮层的发育，因为它是在大脑还在发育的时候首先产生的，它对前额叶皮层内神经元的影响在这个大脑区域进入成熟晚期时比完全成熟时更大。这种增强的有效性使乙酰胆碱处于影响前额叶皮层神经元正常成熟的首要位置，从而对认知功能产生长期影响。然而，许多问题仍然没有答案，因为这种提高效力背后的原因尚不清楚。拟议的研究计划旨在通过确定前额叶皮层发育期间乙酰胆碱信号增强的机制来回答这些问题，反过来，这种乙酰胆碱信号对前额叶皮层内神经元的成熟有什么影响。这项研究计划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发展如何被外部因素（如暴露于压力环境）改变提供基础。

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.