Identifying the physiological correlates of adult-born granule cells in vivo

识别体内成年颗粒细胞的生理相关性

基本信息

批准号：
8978461
负责人：
Kimberly Christian
金额：
$ 24.3万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8978461
关键词：
Acute Adaptive Behaviors Address Adult Affect Age Animals Behavior Birth Brain Cell Aging Cell Survival Cells Cerebral cortex Communities Cytoplasmic Granules Data Data Set Date of birth Developmental Process Electrodes Embryo Employee Strikes Environment Evaluation Exhibits Foundations Functional disorder Genetic Genetic Models Genetic Recombination Heterogeneity Hippocampus (Brain)Implant Investigation Knowledge Learning Light Major Depressive Disorder Mediating Memory Mental disorders Methods Modeling Molecular Mus Nervous system structure Neurons Newborn Infant Opsin Pathology Pattern Physiological Population Preparation Process Property Proteins Reporting Reproducibility Research Resolution Resources Response Latencies Rest Role Seminal Signal Transduction Slice Specificity Stimulus Synaptic plasticity System Tamoxifen Techniques Testing Time Tonic-Clonic Epilepsy Transgenic Model Translating Validation adult neurogenesis base cognitive function cohort critical period dentate gyrus design extracellular genetic approach granule cell in vivo innovation microbial mood regulation mouse model nerve stem cell nervous system disorder neurodevelopment neurogenesis newborn neuron novel optical fiber optogenetics prevent public health relevance reconstruction relating to nervous system research study response

项目摘要

DESCRIPTION (provided by applicant): Adult hippocampal neurogenesis is a dynamic process in which new neurons are continuously generated in the adult brain and integrated into the dentate gyrus, a region that is critical for learning, memory and mood regulation. Dysregulation of this process has been implicated in various psychiatric and neurological disorders, including major depression and epilepsy. Characterizing how these adult- born neurons develop and acquire signaling properties that can affect the local circuitry is important to understand the role of this phenomenon in brain function and pathology. Much of what is known about the electrophysiological properties of these newborn dentate granule cells as they develop has been derived from ex vivo preparations of hippocampal slices. These studies revealed a critical period of plasticity when the cells are around 4 to 6 weeks of age in which they exhibit enhanced synaptic plasticity. This striking observation suggests that there may be a unique, developmentally-regulated role of adult born neurons during a specific time window of maturation. Consequently, a prevalent hypothesis is that newborn granule cells of a particular age exhibit signature patterns of activity in response to environmental stimuli. A direct test of this hypothesis through extracellular single unit recordings has not been possible, however, due to technical limitations that prohibited determining the age of the recorded cell in vivo. To overcome this obstacle, this project is designed to produce a highly specific genetic mouse model (Aim 1) that is amenable to optogenetically-guided tetrode recordings in the dentate gyrus to birthdate, identify and record from single adult-born neurons in freely moving animals (Aim 2). Developing and validating an inducible genetic strategy to target highly proliferative neural progenitors within a narrow time window (i.e. 2 - 4 days) will generate a model in which cohorts of newborn cells can be identified and manipulated with unprecedented precision. This will be a novel resource for the neurogenesis research community to investigate the endogenous function of this population and how its dysregulation may contribute to neural pathology. For the current project, this model will be used to express light-activated opsin channels (channelrhodopsin) in newborn neurons to allow for stimulation and recording of light-responsive putative adult-born granule cells in vivo, via an implanted optical fiber. Completion of these experiments will result in the first description of the firing properties of adult-born granue cells in vivo and the first direct evaluation of whether the critical period of plasticity observedin slice recordings translates to changes in behaviorally relevant neural activity. This innovative approach to address one of the most critical outstanding questions in the field will provide a new genetic model, technique, and dataset to facilitate investigations into the function and dysfunction of adult neurogenesis.

描述（通过应用程序证明）：成人神经发生是降雨，并整合到牙齿回旋中，这对于学习，记忆和情绪调节至关重要。 TOUNDERSTAND在大脑和病理学中的大部分知识。他们的6周大会表现出增强的突触可塑性对于禁止在体内记录的细胞年龄的技术局限性。，在自由移动动物中识别并记录单个成年神经元（AM 2）。可以鉴定出新生细胞的同类，并用前所未有的精度来操纵这将是神经发生研究界的新资源，以研究这种失调的内源性功能，可能会对神经病理进行贡献。新生神经元中的通道rhopopsin允许通过植入的光纤维在体内刺激和记录体内响应性的成年颗粒细胞这些实验将在体内对成年出生的花岗岩细胞的首次驱使，并对批判性可塑性观察到行为相关的神经作用的变化，以解决该领域最关键的杰出模型之一，将提供新的遗传模型之一。成人神经发生的技术功能和功能障碍。