A novel hippocampal GABAergic projection and its potential role in spatial recognition

项目摘要 识别环境的新颖性或熟悉性是空间导航和影响形成和 维护内部空间地图。将环境识别为新的或熟悉的和正在形成的过程 在衰老的啮齿动物和阿尔茨海默病的啮齿动物模型中，适当的空间地图受损 颞叶癫痫，可能反映了患者群体的空间处理缺陷。最近确定的 乳头上区至海马齿状回(Sum→DG)形态的空间新奇信号 在海马体中的空间处理；然而，什么信号影响和空间新奇信号 未知。 本研究探讨了一种新的海马CA1区GABA能投射到总和的投射及其在脑内的潜在作用。 信号空间识别和抑制和空间新奇信号。我称这些细胞为臀部 (海马抑制细胞投射到乳突上区)，我的初步数据表明它们 纤维接近于→DG神经元的总和。这一建议测试了HIPS信号空间识别的假设， 抑制SUM→DG神经元，影响空间加工。我提出了三个目标来分析 髋关节的功能连通性、行为影响和体内活动。我会利用脑片电生理学 结合髋关节的光遗传刺激分析髋关节的连接以求出→、DG神经元和其他 SUM的神经元(目标1)测试髋关节是否有功能性、抑制性连接到SUM，并测试是否 HIPS优先抑制SUM→DG神经元。为了测试髋关节对行为和记忆的影响，我将在体内应用 在空间和非空间熟悉度和新颖性不同的行为任务中刺激髋关节的光遗传学 (目标2)。我还将使用头戴式微型显微镜对髋关节进行活体钙成像 在行为自由的小鼠中，测试髋关节的活动是否反映空间识别(目标3)。 这一提议提供了对新的海马区GABA能投射和参与 空间识别。这项工作也给了我一个极好的机会来训练我对电池、电路和 使用的技术已经在我的赞助人Esther Krook博士的实验室中成功应用- 马格努森。我的赞助人和共同赞助人David Reish博士将在知识和技术方面为我提供全力支持 建议所需的技能，他们每个人都致力于我发展所需的专业技能 从事学术研究的职业。他们的支持与明尼苏达大学的资源相结合 神经科学研究生课程将为我从事独立研究人员的职业生涯做好充分准备。

Project Summary Identifying novelty or familiarity of the environment is required for spatial navigation and influences forming and maintaining internal spatial maps. This process of identifying an environment as novel or familiar and forming the appropriate spatial map is impaired in aging rodents and in rodent models of Alzheimer’s disease and temporal lobe epilepsy, possibly reflecting spatial processing deficits in patient populations. Recently identified spatial novelty signals from the supramammillary area to the hippocampal dentate gyrus (SuM→DG) shape spatial processing in the hippocampus; however, what signals influence SuM spatial novelty signals is unknown. This proposal investigates a novel hippocampal CA1 GABAergic projection to the SuM and its potential role in signaling spatial recognition and suppressing SuM spatial novelty signals. I term these cells HIPS (hippocampal inhibitory cells projecting to the supramammillary area), and my preliminary data indicates their fibers are near SuM→DG neurons. This proposal tests the hypothesis that HIPS signal spatial recognition, inhibit SuM→DG neurons, and influence spatial processing. I am proposing three aims to analyze the functional connectivity, behavioral impact, and in vivo activity of HIPS. I will utilize slice electrophysiology combined with optogenetic stimulation of HIPS to analyze HIPS connections to SuM→DG neurons and other neurons of the SuM (Aim 1) to test if HIPS have functional, inhibitory connections to the SuM and to test if HIPS preferentially inhibit SuM→DG neurons. To test HIPS impact on behavior and memory, I will apply in vivo optogenetics to stimulate HIPS in behavioral tasks which vary spatial and non-spatial familiarity and novelty (Aim 2). I will additionally use head-mounted miniature microscopes to perform in vivo calcium imaging of HIPS in freely behaving mice to test if HIPS’ activity reflects spatial recognition (Aim 3). This proposal provides insight into a novel hippocampal GABAergic projection and potential circuits involved in spatial recognition. This work also gives me the excellent opportunity to train in analysis of cells, circuits, and behavior using techniques which have all been successfully applied in the lab of my sponsor, Dr. Esther Krook- Magnuson. My sponsor and co-sponsor, Dr. David Redish, will fully support me in the knowledge and technical skills required for the proposal, and they are each committed to my development of professional skills needed for an academic research career. Their support combined with the resources of the University of Minnesota Graduate Program in Neuroscience will fully prepare me to pursue a career as an independent researcher.