Neurophysiology of Prefrontal Cortical Development

描述（由申请人提供）：与其他脊椎动物相比，灵长类动物前额叶皮层的大小急剧增加，其进化扩张反映了这些物种的注意力、记忆和执行功能的发展。在发育过程中，前额叶皮层经历了一个漫长的成熟过程，从青春期一直延伸到成年早期。许多精神疾病的发病与前额叶皮层的成熟有关，最明显的是精神分裂症，它在成年早期表现出来。冲动控制也会在成年后得到改善，而未能得到充分发展则与犯罪、药物滥用以及其他健康和社会问题有关。前额叶皮层在青春期和成年早期所经历的生理变化，从而介导认知控制的增强，我们所知甚少。利用最近的方法和概念的进步，我们建议研究青春期后发生的前额皮质生理和功能连接的变化。我们建议使用非人类灵长类动物模型，这将使我们能够在幼年和成年动物的前额叶皮层进行神经生理学记录。我们的研究还将对后顶叶皮层进行取样，这是一个与前额叶皮层相连的区域。这将作为一个控制区，使我们能够确定前额叶皮层成熟的独特之处，也将使我们能够研究前额叶皮层和后顶叶皮层之间功能连接的变化。我们的研究将利用经过训练的猴子来执行需要注意力、工作记忆和执行控制的行为任务。这些实验将提供关于前额皮质发育如何改变其生理反应的见解，这将对理解和治疗与前额皮质成熟问题相关的精神疾病至关重要。

DESCRIPTION (provided by applicant): The size of the prefrontal cortex has increased dramatically in primates compared to other vertebrates and its evolutionary expansion mirrors the development of attention, memory, and executive function in these species. Developmentally, the prefrontal cortex undergoes a long maturation process that extends through puberty and into early adulthood. A number of mental illnesses have onsets linked to the maturation of the prefrontal cortex, most notably schizophrenia, which manifests itself in early adulthood. Impulse control also improves in adulthood, and failure to develop adequately is associated with delinquency, drug abuse, and other conditions of health and social significance. Little is known about the physiological changes that the prefrontal cortex undergoes during puberty and early adulthood so as to mediate increased cognitive control. Taking advantage of recent methodological and conceptual advances, we propose to investigate the changes of prefrontal cortical physiology and functional connectivity that occur after puberty. We propose to use a non-human primate model which will allow us to conduct neurophysiological recordings in the prefrontal cortex of juvenile and adult animals. Our studies will also sample the posterior parietal cortex, an area interconnected with the prefrontal cortex. This will serve as a control area allowing us to determine what is unique about the maturation of the prefrontal cortex, and it will also allow us to study changes of functional connectivity between the prefrontal cortex and posterior parietal cortex. Our study will make use of monkeys trained to perform behavioral tasks that require attention, working memory, and executive control. These experiments will offer insights on how development of the prefrontal cortex alters its physiological responses which will be essential for understanding and treating mental illnesses associated with problems of prefrontal cortical maturation. PUBLIC HEALTH RELEVANCE: The proposed research will determine how the functions of prefrontal cortex neurons change between adolescence and adulthood. Knowledge drawn from these experiments will elucidate the development of higher cognitive processes such as attention and memory, which is necessary for understanding the biological basis of conditions such as Attention Deficit Disorder and mental illnesses such as schizophrenia.