Peptidergic Modulation of NMDA-Receptor Mediated Neurotransmission

NMDA 受体介导的神经传递的肽能调节

基本信息

批准号：
10622524
负责人：
Andres Villu Maricq
金额：
$ 45.8万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10622524
关键词：
Address Alzheimer&apos s Disease Attention Behavior Behavioral Brain Caenorhabditis elegans Cell model Cells Characteristics Confocal Microscopy Defect Dependence Development Disease Electrophysiology (science)Functional disorder G-Protein-Coupled Receptors Genes Genetic Glutamate Receptor Glutamates Goals Hyperactivity Interneurons Intervention Learning Ligands Link Locomotion Measures Mediating Memory Memory Loss Mental disorders Modality Modeling Molecular N-Methyl-D-Aspartate Receptors N-Methylaspartate Nervous System Nervous System Physiology Neurodegenerative Disorders Neurologic Neuromodulator Neurons Neuropeptide Receptor Neuropeptides Neurotransmitters Pathway interactions Peptides Pharmacologic Substance Phenocopy Physiological Processes Pigments Process Production Proteins Receptor Signaling Research Role Signal Pathway Signal Transduction Synapses Synaptic Transmission System Techniques Testing Therapeutic Intervention Time behavioral phenotyping behavioral study experimental study glutamatergic signaling in vivo information processing insight interdisciplinary approach loss of function loss of function mutation model organism mutant nervous system disorder nervous system disorder therapy neuron loss neurotransmission new therapeutic target novel therapeutic intervention novel therapeutics optogenetics pharmacologic postsynaptic presynaptic presynaptic neurons receptor receptor-mediated signaling synaptic function

项目摘要

Synapses control information processing by the nervous system, and dysfunction of synapses is associated with many neurological diseases and neurodegenerative disorders. In all nervous systems, glutamate is the primary excitatory neurotransmitter used to activate neurons. The goals of this study are to provide important, new mechanistic insights into the function of glutamatergic synapses, which will aid in our understanding of information processing by the brain and provide new avenues for the development of pharmaceutical therapies for nervous system disorders. Using a genetic platform based on the nervous system of the model organism C. elegans, we will study how peptide ligands, which signal via G-protein coupled receptors, regulate synaptic function mediated by NMDA-type ionotropic glutamate receptors (NMDARs). Synaptic NMDARs are involved in the pathophysiology of numerous psychiatric and neurological disorders. We propose an integrated multidisciplinary approach that combines in vivo electrophysiological analysis, behavioral studies and optogenetic to study the mechanism of action by which specific neuropeptides regulate NMDAR-mediated synaptic signaling. These studies have particular promise for a deeper understanding of nervous system plasticity, and behaviors such as learning and memory. Our studies will reveal new targets for the development of new drugs and novel therapeutic strategies for disorders of nervous system function.

突触控制神经系统的信息处理，突触功能障碍与之相关患有许多神经系统疾病和神经退行性疾病。在所有神经系统中，谷氨酸是用于激活神经元的主要兴奋性神经递质。这项研究的目标是提供重要的、对谷氨酸突触功能的新机制见解，这将有助于我们理解大脑的信息处理并为药物疗法的开发提供新途径用于神经系统疾病。使用基于模式生物神经系统的遗传平台 C. 在线虫中，我们将研究通过 G 蛋白偶联受体发出信号的肽配体如何调节突触由 NMDA 型离子型谷氨酸受体 (NMDAR) 介导的功能。突触 NMDAR 参与许多精神和神经疾病的病理生理学。我们提出一个综合的结合体内电生理分析、行为研究和光遗传学研究特定神经肽调节 NMDAR 介导的作用机制突触信号传导。这些研究对于更深入地了解神经系统特别有希望可塑性以及学习和记忆等行为。我们的研究将揭示新的发展目标神经系统功能障碍的新药和新治疗策略。