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

项目概要 空间导航需要识别环境的新颖性或熟悉性，并影响形成和形成 维护内部空间地图。这个识别环境是新的还是熟悉的并形成的过程 衰老啮齿动物和阿尔茨海默病啮齿动物模型中适当的空间图受到损害， 颞叶癫痫，可能反映了患者群体的空间处理缺陷。最近发现 从乳头上区到海马齿状回（SuM→DG）形状的空间新颖性信号 海马体的空间处理；然而，影响 SuM 空间新颖性信号的信号是 未知。 该提案研究了一种新的海马 CA1 GABAergic 投射到 SuM 及其在 发出空间识别信号并抑制 SuM 空间新奇信号。我将这些细胞称为 HIPS （海马抑制细胞投射到乳头上区域），我的初步数据表明它们 纤维靠近 SuM→DG 神经元。该提案测试了 HIPS 信号空间识别的假设， 抑制SuM→DG神经元，影响空间处理。我提出三个目标来分析 HIPS 的功能连接、行为影响和体内活性。我将利用切片电生理学 结合HIPS的光遗传学刺激来分析HIPS与SuM→DG神经元和其他神经元的连接 SuM 的神经元（目标 1），以测试 HIPS 是否与 SuM 具有功能性、抑制性连接，并测试是否 HIPS 优先抑制 SuM→DG 神经元。为了测试 HIPS 对行为和记忆的影响，我将在体内应用 光遗传学在不同空间和非空间熟悉度和新颖性的行为任务中刺激 HIPS （目标 2）。我还将使用头戴式微型显微镜进行 HIPS 体内钙成像 在自由行为的小鼠中测试 HIPS 的活动是否反映了空间识别（目标 3）。 该提案提供了对新型海马 GABA 能投射和参与的潜在电路的深入了解 空间识别。这项工作还为我提供了接受细胞、电路和细胞分析培训的绝佳机会。 使用已在我的资助者 Esther Krook 博士的实验室中成功应用的技术进行行为- 马格努森。我的赞助商和共同赞助商 David Redish 博士将在知识和技术方面全力支持我 提案所需的技能，并且他们每个人都致力于我发展所需的专业技能 从事学术研究事业。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.