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Functional dissection of a radial subdivision among hippocampal pyramidal cells

海马锥体细胞径向细分的功能解剖

基本信息

批准号：
8957381
负责人：
Nathan B Danielson
金额：
$ 4.39万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8957381
关键词：
Alzheimer&apos s Disease Animals Area Behavior Behavioral Brain Calcium Cataloging Catalogs Cells Chronic Code Complex Data Development Dissection Distal Dorsal Environment Event Exhibits Genetic Goals Head Hippocampal Formation Hippocampus (Brain)Image Interneurons Learning Life Light Mediating Memory Methods Monitor Mus Nature Neurons Operative Surgical Procedures Output Pathology Patients Pattern Pharmacogenetics Phase Population Preparation Process Property Pyramidal Cells Radial Relative (related person)Research Resolution Retrieval Rodent Role Schizophrenia Societies Structure Testing Time Work awake base cell type conditioned fear dentate gyrus developmental genetics flexibility in vivo information processing learned behavior lens nervous system disorder optical imaging public health relevance relating to nervous system segregation submicron two-photon way finding

项目摘要

DESCRIPTION (provided by applicant): The capacity for memory is one of the most profound features of the mammalian brain, and the proper encoding and retrieval of information are the processes that form the basis of learning. The centrality of learning and memory to all aspects of mammalian life underscores the devastating nature of degenerative neurological disorders, such as Alzheimer's disease and schizophrenia that impair the hippocampus and compromise these processes. Although the hippocampal formation is one of the most extensively studied structures in the brain, the circuit mechanisms underlying its normal function remain elusive. Hippocampal principal cells form complex representations of the external environment, but in stark contrast to the diversity of inhibitory interneurons catalogued and despite the apparent need for functional segregation, they are largely considered a homogeneous population. The goal of this proposed research is to investigate functional segregation within the pyramidal cell population at the output node of the hippocampus, area CA1. In particular, given known developmental, genetic, and connectivity differences between superficial and deep cells in this region, we aim to explore the functional differences between these subpopulations and their relative contributions to learning and memory. This proposal implements numerous recent advances in optical imaging and genetic perturbation methods in the mouse, allowing us to longitudinally monitor and manipulate the activity of large populations of hippocampal neurons with submicron spatial resolution over days to weeks as the animal engages in various learning paradigms. In area CA1 principal cells form representations of the external world through their coordinated firing patterns. While spatial representations of static environments persist over long time periods, firing patterns in the CA1 principal cell population change dramatically over the course of learning. This proposal will test the hypothesis that superficial and deep CA1 principal cells demonstrate different coding dynamics during spatial navigation behaviors and learning tasks. Preliminary data from a head-fixed spatial navigation task suggests that spatial representations in the superficial CA1 pyramidal cell population are highly stable over many days, while firing patterns in the deep population are far more variable, suggesting a functional difference between these subpopulations and perhaps satisfying the need for both stability and flexibility in hippocampal codes. This proposal will also implement pharmacogenetic manipulations to test the hypothesis that coding differences between these subpopulations are the causal basis for differential contributions to learning and memory. In summary this work will use chronic head-fixed two- photon imaging of different subpopulations of CA1 pyramidal cells during learning in the awake rodent to further our understanding of functional subdivision in the hippocampal circuit.