Monitoring presynaptic release of neuropeptides in awake behaving animals

监测清醒行为动物的突触前神经肽释放

• 批准号: 10517245
• 负责人: Sung Han
• 金额: $ 204.52万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10517245
• 关键词: Address; Affective; Animal Behavior; Animals; Anorexia Nervosa; Anxiety; Anxiety Disorders; Arousal; Behavior; Biogenic Amines; Biological Models; Brain; Brain Diseases; Calcitonin Gene-Related Peptide; Catecholamines; Cell Line; Chimeric Proteins; Cognitive; Communication; Cre driver; Dense Core Vesicle; Development; Disease; Drug Targeting; Emotional; Engineering; Etiology; Event; Fiber; Fright; Functional disorder; Genetic; Goals; In Vitro; Integral Membrane Protein; Learning; Membrane Proteins; Memory; Metabolism; Monitor; Mus; Neuroendocrine Cell; Neuromodulator; Neuromodulator Receptors; Neurons; Neuropeptides; Neurophysiology - biologic function; Neurotransmitters; Oxytocin; PHluorin; Pain; Performance; Pharmacology; Photometry; Physiological; Presynaptic Terminals; Proteins; Proxy; Public Health; Recycling; Regulation; Research; Rewards; Role; Sex Behavior; Signal Transduction; Slice; Social Behavior; Synaptic Transmission; Synaptic Vesicles; System; Techniques; Testing; Validation; Variant; Viral Vector; Work; addiction; awake; base; cell type; cognitive process; cytochrome b561; design; druggable target; feeding; gain of function; improved; in vivo; innovation; loss of function; monoamine; nervous system disorder; neural circuit; neuropsychiatric disorder; novel; peptidylglycine alpha-amidating monooxygenase; postsynaptic; presynaptic; quantum; receptor; sensor; tool

ABSTRACT Neuromodulators, such as neuropeptides and biogenic amines are produced and released by neurons to communicate with each other. They act as neurotransmitters, as well as neuromodulators, to profoundly influence the function of neural circuits, thereby regulating critical brain functions, including arousal, feeding, metabolism, social behavior, fear/anxiety, learning/memory, reward, and sexual behaviors. Dysfunction in neuromodulator signaling is associated with many neurological and neuropsychiatric disorders. Therefore, understanding the mechanism of neuromodulator functions in the brain is important for understanding brain disorders. Among these, neuropeptides are by far the most diverse class of neuromodulators in the brain, and they are involved in a range of physiological, emotional, and cognitive processes in the brain. Although more than 100 neuropeptides and their downstream receptors have been discovered, circuit-based mechanisms of neuropeptide functions have not been adequately explored. This is primarily because the field lacks tools for monitoring the release of neuropeptides in a temporally precise manner as animals perform behaviors. To fill this void, the research proposed here will develop a novel quantitative technique for detecting neuropeptide release from the presynaptic terminals in awake behaving mice. This proposal will develop a sensor that detects the release of dense-core vesicles that specifically packages neuropeptides in the axonal terminals. This innovative approach will allow us to monitor the presynaptic release of essentially all neuropeptides, thereby addressing fundamental questions about the neuropeptidergic regulation of brain functions.

抽象的 神经调节剂，如神经肽和生物胺，由神经元产生和释放以相互沟通。它们作为神经递质和神经调节剂，深刻影响神经回路的功能，从而调节关键的大脑功能，包括唤醒、进食、新陈代谢、社会行为、恐惧/焦虑、学习/记忆、奖励和性行为。神经调节信号传导功能障碍与许多神经系统和神经精神疾病有关。因此，了解大脑中神经调节剂功能的机制对于了解大脑疾病非常重要。其中，神经肽是迄今为止大脑中最多样化的一类神经调节剂，它们参与大脑中的一系列生理、情感和认知过程。尽管已经发现了 100 多种神经肽及其下游受体，但神经肽功能的基于电路的机制尚未得到充分探索。这主要是因为该领域缺乏在动物行为时以时间精确的方式监测神经肽释放的工具。为了填补这一空白，本文提出的研究将开发一种新颖的定量技术，用于检测清醒行为小鼠突触前末梢释放的神经肽。该提案将开发一种传感器，用于检测专门包装轴突末端神经肽的致密核心囊泡的释放。这种创新方法将使我们能够监测基本上所有神经肽的突触前释放，从而解决有关大脑功能的神经肽能调节的基本问题。