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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.

摘要