The Role of Cortical Neurotransmitter Systems in Human and Nonhuman Primate Brain Evolution

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。目前人们对人类和动物大脑的不同知之甚少。虽然人类的大脑异常大，但我们也知道，即使是很小的结构变化，因为太小而无法通过大脑宏观结构的检查检测到，也会极大地影响行为。神经递质是塑造人类思维进化的有力候选者，因为(1)它们在大脑特定区域内的活动支持更高的认知功能，包括学习、记忆和语言；(2)它们的消耗导致认知功能下降；(3)人类神经病理与极端认知缺陷，如阿尔茨海默氏症、帕金森病和精神分裂症，都与神经递质密度的特定降低有关。有可能对神经递质的依赖强调了人类的高级智力，但同时也使我们在这些毁灭性的疾病过程中变得特别脆弱。如果神经递质促进了人类大脑的进化，那么在涉及高级认知功能的大脑区域中，神经递质轴突的密度更高就可以证明这一点。为了验证这一假设，将比较人类和非人类灵长类动物大脑中的多巴胺、血清素、乙酰胆碱和去甲肾上腺素神经递质密度。要分析的区域包括语言和对认知和情绪处理至关重要的高阶关联区域。初级运动皮层将起到控制作用。对每种神经递质进行免疫染色的切片将使用体视学方法进行定量。这个项目的智力价值将包括获得关于灵长类动物大脑进化的宝贵见解，以及进一步我们对支持人类复杂思维和语言的神经解剖学基础的理解。这项工作也可能阐明与药理学和临床实践相关的神经退行性疾病的人类特异性靶点。更广泛的影响包括灵长类动物大脑部分的档案，研究生和本科生的跨学科培训，以及与麦克奈尔学者计划合作，促进来自代表性不足群体的学生的高等教育，为研究生学习做准备。该研究将提供一名研究生和一名本科生支持，并雇用一名专业的全职技术人员。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Little is currently known about how human and animal brains differ. While the human brain is unusually large, it is also known that even small structural changes, too small to be detected by an examination of the brain's macrostructure, can greatly impact behavior. Neurotransmitters are compelling candidates for shaping the evolution of the human mind because (1) their actions within specific areas of the brain support higher cognitive functions, including learning, memory, and language, (2) their depletion results in decreased cognitive function, and (3) human neuropathologies with extreme cognitive deficits such Alzheimer's, Parkinson's, and schizophrenia are associated with specific decreases in neurotransmitter densities. It is possible that a dependence on neurotransmitters underscores human advanced intellect, but at the same time renders us uniquely vulnerable to these devastating disease processes. If neurotransmitters contributed to human brain evolution, this would be demonstrated by a higher density of neurotransmitter axons in brain regions involved in advanced cognitive functions. To test this hypothesis, dopamine, serotonin, acetylcholine, and norepinephrine neurotransmitter densities will be compared in human and nonhuman primate brains. Areas to be analyzed include language and higher-order association regions critical to cognitive and emotional processing. Primary motor cortex will serve as a control. Sections immunostained for each neurotransmitter will be quantified using stereologic methods. Intellectual merit of this project will include gaining valuable insight about primate brain evolution in addition to furthering our understanding of the neuroanatomical substrates that have emerged to support complex thought and language in humans. This work may also elucidate human-specific targets for neurodegenerative diseases relevant to pharmacology and clinical practice. Broader impacts include an archive of primate brain sections, interdisciplinary training of graduate and undergraduate students and collaboration with the McNair Scholar Program to promote the advanced education of students from underrepresented groups in preparation for post-graduate study. The research will provide support for one graduate and one undergraduate student as well as employ one professional, full-time technician.