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.

海马体是一种大脑结构，对于长期记忆的存储和回忆以及空间导航至关重要。它也是唯一能够在人的一生中保持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。该项目将通过在神经解剖学、基因表达和遗传学水平上将人类的海马体与我们现存的最亲近的非人类灵长类动物的海马体进行比较，来研究人类记忆的起源。这项研究将为某些人类特有的记忆相关能力的神经生物学基础以及可能推动其出现的生态因素提供新的见解。此外，该项目将确定神经生物学目标，这些目标可能使人类特别容易受到某些已知影响海马体的神经系统疾病和紊乱（例如阿尔茨海默病、自闭症谱系障碍）的影响。该项目的数据可能为人类大脑形态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指导和研究经验，研究人员将参与公共科学推广活动，以促进对神经科学、遗传学和人类进化的理解。虽然海马体是所有哺乳动物长期记忆的核心，但只有人类知道它还介导情景记忆，即回忆特定个人经历和想象未来事件的能力。这可能首先出现在我们的古人类祖先身上，以满足日益具有挑战性的环境、扩大的活动范围和新颖的狩猎/觅食策略的需求。最近的证据表明，与其他灵长类动物相比，人类的整个海马体在相对大小、神经元结构和分布以及基因表达方面已经变得进化专门化。然而，众所周知，海马体由分子和功能上不同的子区域组成。因此，该项目将从神经解剖学、基因表达和基因型方面研究人类和非人类灵长类动物海马体的进化。将估计海马亚区的体积比例和成人海马神经发生的程度，并将生态变量与神经解剖学测量相关联以测试神经生态学关系。将生成海马亚区的全转录组基因表达数据并用于识别在人类中差异表达的基因。将测试基因的蛋白质编码和调控区域以进行正选择。