Group II metabotropic glutamate receptors in the aging brain

衰老大脑中的 II 类代谢型谷氨酸受体

基本信息

批准号：
9353277
负责人：
CHARLES C LEE
金额：
$ 7.4万
依托单位：
LOUISIANA STATE UNIV A&M COL BATON ROUGE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9353277
关键词：
Age Age of Onset Age-Months Aging Anatomy Animal Testing Animals Attention Auditory Auditory Brainstem Responses Auditory area Auditory system Beavers Behavior Biological Assay Biological Models Brain Brain region Cells Cognitive deficits Data Deterioration Disease Equilibrium Etiology Foundations Future Glutamates Goals Health Hearing Immunohistochemistry Impairment In Vitro Investigation Knowledge Lasers Link Mediating Metabotropic Glutamate Receptors Methods Mission Molecular Mouse Strains Neocortex Neurons Outcome Pathologic Pathway interactions Pattern Perception Pharmacology Physiological Pilot Projects Preparation Productivity Prosencephalon Public Health Quality of life Receptor Activation Research Role Scanning Sensory Slice Societies Synapses Testing Time United States National Institutes of Health Visual Visual Cortex age related aging brain base experience experimental study hearing impairment improved in vivo innovation interest mouse model nervous system disorder neural circuit neurophysiology novel patch clamp prevent prospective receptor receptor expression relating to nervous system response therapeutic target

项目摘要

ABSTRACT The deterioration of neural circuits in the brain is a contributing factor to the perceptual deficits associated with aging. The long-term goals of our research are to understand the molecular and neural alterations that underlie age-related perceptual impairments. The primary objective of this R03 pilot proposal is to characterize the molecular neuropharmacological alterations to Group II metabotropic glutamate receptors (mGluRs), which enable glutamatergic inhibition at forebrain synapses. The central hypothesis is that the expression of these Group II mGluRs is altered with age in the neocortex. This is rationalized to result in changes to the balance of excitation and inhibition in the neocortex and contribute to the emergence of age-related sensory perceptual deficits. Several neuroanatomical and neurophysiological features of these receptors have been identified, which forms the basis for the proposed investigation. The specific aims of this project are to characterize the alterations to Group II mGluRs in the neocortex with age by examining: 1) changes in the neuroanatomical expression patterns of these receptors and 2) alterations to forebrain neurophysiological responses mediated by pharmacological activation of these receptors. The proposed experiments are expected to identify the age- related changes to Group II mGluRs in the neocortex and guide our future investigations aimed at directly linking these receptor alterations with the perceptual deficits experienced during aging and ultimately restoring normal behavior in this model system. These experiments will have a positive impact by illuminating the potentially important role of Group II mGluRs in age-related perceptual deficits and as a prospective therapeutic target for these conditions.

抽象的大脑中神经回路的恶化是导致与感知缺陷有关的因素老化。我们研究的长期目标是了解分子和神经改变基础与年龄有关的感知障碍。该R03试点建议的主要目的是表征对II组代谢型谷氨酸受体（MGLURS）的分子神经药物改变，该改变在前脑突触中启用谷氨酸能抑制。中心假设是这些的表达 II组mglurs随着新皮层的年龄而改变。这是合理化的，从而改变了新皮层的激发和抑制作用，并导致与年龄相关的感觉的出现缺陷。这些受体的几种神经解剖学和神经生理特征已被鉴定出来，这构成了拟议调查的基础。该项目的具体目的是表征通过检查新皮层中II组mglurs的改变：1）神经解剖学的变化这些受体的表达模式和2）介导的前脑神经生理反应的改变通过这些受体的药理激活。提出的实验有望确定年龄新皮层中II组MGLURS的相关更改，并指导我们的未来研究直接将这些受体改变与衰老期间遇到的感知缺陷联系起来并最终恢复此模型系统中的正常行为。这些实验将通过阐明 II组MGLURS在与年龄有关的感知缺陷中的潜在重要作用，并作为前瞻性这些条件的治疗靶标。