Molecular mechanisms underlying cholinergic signaling in developing neurons

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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.