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：
10280822
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/10280822
关键词：
Address Alzheimer&apos s Disease Animal Model 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 Lead Learning Ligands Link Locomotion Measures Mediating Memory Memory Loss Mental disorders Modality Modeling Molecular N-Methyl-D-Aspartate Receptors N-Methylaspartate Nervous System Physiology Nervous system structure Neurodegenerative Disorders Neurologic Neuromodulator Neurons Neuropeptide Receptor Neuropeptides Neurotransmitters Peptides Pharmacologic Substance Pharmacology Phenocopy Physiological Processes Pigments Process Production Proteins Research Role Signal Pathway Signal Transduction Synapses Synaptic Transmission System Techniques Testing Therapeutic Intervention Time base behavioral phenotyping behavioral study experimental study glutamatergic signaling in vivo information processing insight interdisciplinary approach loss of function loss of function mutation mutant nervous system disorder nervous system disorder therapy neuron loss neurotransmission new therapeutic target novel therapeutic intervention novel therapeutics optogenetics postsynaptic presynaptic presynaptic neurons receptor 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.

突触控制信息处理通过神经系统处理，突触功能障碍与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一级兴奋性神经递质。这项研究的目标是提供重要的对谷氨酸能突触功能的新机械洞察力，这将有助于我们理解大脑的信息处理，并为开发药物疗法提供新的途径用于神经系统疾病。使用基于模型生物体的神经系统的遗传平台。秀丽隐杆线，我们将研究如何通过G蛋白偶联受体发出信号的肽配体调节突触 NMDA型离子型谷氨酸受体（NMDAR）介导的功能。突触NMDAR参与许多精神病和神经系统疾病的病理生理学。我们提出了一个综合的多学科方法结合了体内电生理学分析，行为研究和光遗传学研究作用机理，特定神经肽调节NMDAR介导的作用机理突触信号传导。这些研究特别有望深入了解神经系统可塑性以及学习和记忆等行为。我们的研究将揭示开发的新目标神经系统功能疾病的新药和新型治疗策略。