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。 目前对人类和动物大脑的差异知之甚少。虽然人类的大脑非常大，但我们也知道，即使是很小的结构变化，太小以至于无法通过检查大脑的宏观结构来检测，也会极大地影响行为。神经递质是塑造人类思维进化的引人注目的候选者，因为（1）它们在大脑特定区域内的作用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，以及（3）具有极端认知缺陷的人类神经病理学，如阿尔茨海默氏症，帕金森氏症，和精神分裂症与神经递质密度的特定降低有关。对神经递质的依赖可能强调了人类的高级智力，但同时也使我们特别容易受到这些毁灭性疾病的影响。如果神经递质促进了人类大脑的进化，这将通过参与高级认知功能的大脑区域中更高密度的神经递质轴突来证明。为了验证这一假设，我们将比较人类和非人类灵长类动物大脑中多巴胺、血清素、乙酰胆碱和去甲肾上腺素神经递质的密度。待分析的区域包括对认知和情感处理至关重要的语言和高阶关联区域。初级运动皮层将作为对照。将使用体视学方法对每种神经递质的免疫染色切片进行定量。该项目的智力价值将包括获得有关灵长类动物大脑进化的宝贵见解，以及进一步了解支持人类复杂思维和语言的神经解剖学基质。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切片的档案，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，以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。 该研究将为一名研究生和一名本科生提供支持，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.