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

点击翻译按钮获取中文摘要

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.