Normal and Pathological Function of the Dentate Gyrus

齿状回的正常和病理功能

基本信息

批准号：
8712585
负责人：
DOUGLAS A COULTER
金额：
$ 36.27万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8712585
关键词：
Action Potentials Adult Animal Model Animals Area Behavior Birth Brain Calcium Cells Code Cognitive Cognitive deficits Comorbidity Control Animal Decision Making Development Dyes Emotions Environment Epilepsy Episodic memory Exhibits Feedback Frequencies Gene Targeting Generations Hippocampus (Brain)Image Imaging Techniques In Vitro Individual Interneurons Learning Limbic System Mediating Memory Moods Nature Neurons Patients Pattern Play Population Probability Process Property Regulation Relative (related person)Reporter Role Seizures Series Shapes Specificity Stochastic Processes Structure Techniques Testing Time Transgenic Organisms cognitive function dentate gyrus effective therapy entorhinal cortex experience granule cell in vivo insight memory process nerve supply optogenetics patch clamp response therapy development voltage

Action Potentials Adult Animal Model Animals Area Behavior Birth Brain Calcium Cells Code Cognitive Cognitive deficits Comorbidity Control Animal Decision Making Development Dyes Emotions Environment Epilepsy Episodic memory Exhibits Feedback Frequencies Gene Targeting Generations Hippocampus (Brain)Image Imaging Techniques In Vitro Individual Interneurons Learning Limbic System Mediating Memory Moods Nature Neurons Patients Pattern Play Population Probability Process Property Regulation Relative (related person)Reporter Role Seizures Series Shapes Specificity Stochastic Processes Structure Techniques Testing Time Transgenic Organisms cognitive function dentate gyrus effective therapy entorhinal cortex experience granule cell in vivo insight memory process nerve supply optogenetics patch clamp response therapy development voltage

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项目摘要

DESCRIPTION (provided by applicant): The dentate gyrus is a critical contributor in the cognitive functions of the hippocampus. The principal cells of the dentate gyrus, dentate granule cells, exhibit firing in small subpopulations during execution of cognitive tasks, consistent with the process of sparse coding. Sparse coding is a stochastic process. This may not apply to the dentate gyrus, since small populations of cells exhibit preferential activation in multiple environments, while others remain persistently silent, a deterministic firing pattern. The mechanisms responsible for this are entirely unknown, but the birth of new granule cells in the adult brain may contribute. The dentate gyrus also regulates pathological activation of the limbic system. This function, when compromised, may contribute to epilepsy development. In patients with epilepsy, in addition to seizures, there are cognitive deficits that arise associated with damage to the dentate gyrus and other hippocampal structures. In this proposal, we will utilize advanced imaging, patch clamp, optogenetic, and transgenic techniques to test the hypothesis that sparse, deterministic firing of granule cells emerges as a specific consequence of tailored inhibitory function within the dentate gyrus, and this exhibits significant erosion in animals with epilepsy. We propose to characterize network firing in the dentate gyrus, determine the contributions of adult born granule cells to these firing properties, and examine dentate network activation in animals with epilepsy. Little is known about the mechanisms mediating cellular activation in the dentate gyrus, and how epilepsy development may erode these processes. In addition to seizures, patients with epilepsy exhibit severe cognitive co-morbidities, including deficits in emotion, mood, and learning and memory, typically thought of as limbic system functions. Understanding how epilepsy development alters limbic circuit properties is important both in targeting new therapies for seizure amelioration, and in developing treatments to reduce co-morbid conditions associated with seizure disorders.

描述（由申请人提供）：齿状回是海马认知功能的关键因素。在执行认知任务期间，齿状回，齿状颗粒细胞的主要细胞在小亚群中表现出发射，这与稀疏编码过程一致。稀疏编码是一个随机过程。这可能不适用于齿状回的，因为小细胞种群在多种环境中表现出优先激活，而其他细胞则保持持久的静音，这是确定性的射击模式。负责这一点的机制是完全未知的，但是成人大脑中新的颗粒细胞的诞生可能会产生。齿状回还调节边缘系统的病理激活。当受损时，此功能可能有助于癫痫发育。在癫痫患者中，除了癫痫发作外，还存在与齿状回和其他海马结构损害有关的认知缺陷。在该提案中，我们将利用先进的成像，斑块夹，光遗传学和转基因技术来检验以下假设：稀疏的，确定性的颗粒细胞发射是作为齿状回旋中量身定制抑制功能的特定结果，并且这表现出与动物在动物中具有重大侵蚀的侵蚀癫痫。我们建议表征齿状回中的网络射击，确定成年生颗粒细胞对这些发射特性的贡献，并检查具有癫痫动物的动物中的齿状网络激活。关于介导齿状回中介导细胞活化的机制，以及癫痫发育如何侵蚀这些过程。除癫痫发作外，癫痫患者还表现出严重的认知合并症，包括情绪，情绪和学习和记忆和记忆的缺陷，通常被视为边缘系统功能。了解癫痫发育如何改变边缘电路的特性对于针对癫痫发作的新疗法以及开发疗法以减少与癫痫发作疾病相关的合并状况很重要。