Presynaptic NMDAR Function in the Hippocampus

海马突触前 NMDAR 功能

• 批准号: 9186418
• 负责人: Pablo Lituma
• 金额: $ 4.4万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9186418
• 关键词: AMPA Receptors; Acetylcholine; Action Potentials; Acute; Alzheimer' s Disease; Anatomy; Autistic Disorder; Autoreceptors; Axon; Binding; Brain; Calcium; Cells; Communication; Cyclic AMP-Dependent Protein Kinases; Development; Electrophysiology (science); Epilepsy; Functional disorder; Glutamates; Goals; Hippocampus (Brain); Image; Investigation; Ions; Kainic Acid Receptors; Knowledge; Laboratories; Laser Microscopy; Learning; Link; Long-Term Depression; Long-Term Potentiation; Measures; Mediating; Membrane Potentials; Memory; Molecular; Molecular Biology; N-Methyl-D-Aspartate Receptors; NMDA receptor A1; Neuromodulator; Neurons; Nicotine; Pattern; Permeability; Pharmacology; Phosphotransferases; Presynaptic Receptors; Property; Protein Kinase; Pyramidal Cells; Rattus; Regulation; Rest; Rodent Model; Role; Schizophrenia; Signal Transduction; Slice; Structure; Synapses; Synaptic Transmission; Synaptic plasticity; Testing; Therapeutic; Training; Work; alpha-bungarotoxin receptor; cognitive function; detector; granule cell; in vivo; insight; knock-down; mossy fiber; nervous system disorder; neuroimaging; neuropsychiatry; neuroregulation; neurotransmission; neurotransmitter release; novel; novel therapeutics; optogenetics; patch clamp; postsynaptic; presynaptic; public health relevance; receptor; relating to nervous system; response; skills; synaptic function; trafficking; transmission process; two-photon

 DESCRIPTION (provided by applicant): The goal of this project is to elucidate the role of presynaptic NMDA receptor (preNMDAR) function in the hippocampus, a key brain structure involved in learning and memory. NMDA receptor activity is crucial for neuronal communication and normal brain function. Consequently, NMDA receptor dysfunction is implicated in several neurological disorders such as epilepsy, schizophrenia, autism, and Alzheimer's disease. This proposal incorporates training in a number of advanced laboratory skills in the fields of electrophysiology, molecular biology, and state of the art neuroimaging in order to conduct a detailed investigation of preNMDAR function in the hippocampus. To study the molecular and functional properties of preNMDARs we will use in vivo combinatory molecular knockdown-optogenetic strategies in addition to complimentary whole-cell patch clamp recordings using selective pharmacology and calcium imaging. In doing so, we will also examine the contribution of preNMDARs to hippocampal synaptic transmission and plasticity. Lastly, we will evaluate the ability of molecular signaling kinases and neuromodulators to regulate preNMDAR function during certain conditions of neural activity. In determining the role of preNMDAR function in the hippocampus our work will reveal novel cellular and molecular mechanisms that support learning and memory. In addition, we may contribute significant insights of synaptic mechanisms that could underlie NMDAR-associated brain deficits.

 描述（由申请人提供）：该项目的目标是阐明海马体中突触前 NMDA 受体 (preNMDAR) 功能的作用，海马体是参与学习和记忆的关键大脑结构，对于神经元通讯和正常大脑至关重要。经测试，NMDA 受体功能障碍与多种神经系统疾病有关，例如癫痫、精神分裂症、自闭症和阿尔茨海默氏病。该提案包括培训。掌握电生理学、分子生物学和最先进的神经影像学领域的许多先进实验室技能，以便对海马中的 preNMDAR 功能进行详细研究。为了研究 preNMDAR 的分子和功能特性，我们将在体内使用。除了使用选择性药理学和钙成像的免费全细胞膜片钳记录之外，组合分子敲除-光遗传学策略在此过程中，我们还将检查前 NMDAR 对海马的贡献。最后，我们将评估分子信号激酶和神经调节剂在某些神经活动条件下调节 preNMDAR 功能的能力。在确定 preNMDAR 功能在海马中的作用时，我们的工作将揭示支持的新细胞和分子机制。此外，我们还可以对 NMDAR 相关大脑缺陷的突触机制做出重要的见解。