Doctoral Dissertation Research: Human memory, adult neurogenesis, and the evolution of the hippocampus

博士论文研究：人类记忆、成人神经发生和海马体的进化

• 批准号: 1650865
• 负责人: Chet Sherwood
• 金额: $ 3.15万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2018-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1650865&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Human; memory

The hippocampus is a brain structure that is critical for the storage and recall of long-term memory as well as spatial navigation. It is also one of the only brain structures that maintains the ability to generate new neurons throughout one's lifetime, a feature necessary for effective long-term memory. This project will investigate the origins of human memory by comparing the hippocampus of humans to those of our closest living non-human primate relatives at the levels of neuroanatomy, gene expression, and genetics. This research will provide novel insights into the neurobiological basis of certain human-specific memory-related abilities and the ecological factors that may have driven their emergence. Furthermore, this project will identify neurobiological targets that may render humans uniquely susceptible to certain neurological diseases and disorders known to affect the hippocampus (e.g., Alzheimer's disease, Autism spectrum disorder). Data from this project may inform further research and discoveries on human brain form and function. The project will support undergraduate mentoring and research experiences, and the investigators will engage in public science outreach to promote understanding of neuroscience, genetics and human evolution.While the hippocampus is central to long-term memory in all mammals, only in humans is it known to additionally mediate episodic memory, the capacity to recall specific personal experiences and imagine future events. This may have first emerged in our hominin ancestors to meet the demands of increasingly challenging environments, expanded home ranges, and novel hunting/foraging strategies. Recent evidence suggests that the human whole-hippocampus has become evolutionarily specialized compared to those of other primates in terms of relative size, neuronal structure and distribution, and gene expression. However it is well known that the hippocampus is composed of molecularly and functionally distinct subfields. This project will therefore investigate the evolution of the hippocampus in humans and non-human primates in terms of neuroanatomy, gene expression, and genotype. Volumetric proportions of hippocampal subfields and degree of adult hippocampal neurogenesis will be estimated, and ecological variables will be correlated with neuroanatomical measures to test for neuroecological relationships. Whole-transcriptome gene expression data of hippocampal subfields will be generated and used to identify genes that are differentially expressed in humans. Protein-coding and regulatory regions of genes will be tested for positive selection.

海马是一种大脑结构，对于长期记忆和空间导航的存储和回忆至关重要。它也是唯一保持在整个人一生中生成新神经元的能力的大脑结构之一，这是有效的长期记忆所必需的功能。该项目将通过将人类的海马与我们最亲密的非人类灵长类动物亲戚的海马来研究人类记忆的起源，在神经解剖学，基因表达和遗传学水平上。这项研究将为某些与人类特定记忆有关的能力的神经生物学基础提供新的见解以及可能导致其出现的生态因素。此外，该项目将确定神经生物学靶标，这些靶标可能会使人类易受某些神经系统疾病和已知影响海马的疾病（例如，阿尔茨海默氏病，自闭症谱系障碍）的独特感染。该项目的数据可能会为人脑形式和功能的进一步研究和发现提供信息。该项目将支持本科生的指导和研究经验，研究人员将参与公共科学范围，以促进对神经科学，遗传学和人类进化的理解。尽管海马在所有哺乳动物中都是长期记忆的核心，但只有在人类中，它才众所周知，它众所周知，它可以使人记忆和想象特定的个人经历和想象未来的未来事件。这可能首先在我们的人类祖先中出现，以满足越来越具有挑战性的环境，扩大的家庭范围以及新颖的狩猎/觅食策略的需求。最近的证据表明，就相对大小，神经元结构和分布以及基因表达而言，与其他灵长类动物相比，人类的全-hampocamp已在进化上变得专门化。然而，众所周知，海马由分子和功能上不同的子场组成。因此，该项目将在神经解剖学，基因表达和基因型方面研究人类和非人类灵长类动物中海马的演变。将估计海马子场的体积比例和成年海马神经发生程度，生态变量将与神经解剖学措施相关，以测试神经生态学关系。将生成海马子场的全转录组基因表达数据，并用于鉴定在人类中差异表达的基因。基因的蛋白质编码和调节区域将进行阳性选择。