Determining Fundamental Properties of Neurotransmitter Switching in Adult Mammals

确定成年哺乳动物神经递质转换的基本特性

• 批准号: 10152684
• 负责人: NICHOLAS CANADAY SPITZER
• 金额: $ 55.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10152684
• 关键词: Address; Adult; Affect; Animal Behavior; Automobile Driving; Behavior; Behavioral; Brain; Brain region; Clinical; Cognitive; Emotions; Environment; Future; Genetic; Goals; Intelligence; Knowledge; Life; Light; Link; Mammals; Memory; Nervous system structure; Neurotransmitters; Odors; Patients; Pattern; Perception; Property; Reporter; Research; Role; Spinal Cord; Stimulus; Synapses; Testing; experience; experimental study; novel; postsynaptic; prevent; programs; receptor; response; sensory stimulus

Project Summary Abstract: Our perceptions, behaviors, emotions, memories and intelligence depend on the appropriate synthesis and release of specific neurotransmitters in the brain. Transmitter identity is initially established by genetic programs. It has been thought that transmitters are fixed and invariant throughout life and that the plasticity of the nervous system consists largely of changes in the strength and number of synapses. We have found that experimental perturbations of spontaneous electrical activity and natural changes in sustained sensory stimuli such as ambient light or odors respecify transmitter identity in the spinal cord and brain in the developing nervous system, leading to matching changes in postsynaptic transmitter receptor specification and changes in animal behavior. Strikingly we found that transmitter switching and receptor matching also occur in the adult mammalian brain in response to sustained sensory stimuli and can regulate behavior. These discoveries contrast sharply with the general view of transmitter constancy and identify another way that the nervous system adapts to the environment. Here we describe experiments to determine how many transmitter switches are induced by a single environmental stimulus and how many brain regions are affected. There is increasing understanding that the brain is a widely linked network and that single perturbations alter activity throughout the brain. It is important to address this issue in order to understand better the basis of changes in behavior in response to the sustained stimuli that are major determinants of our conduct. A major part of our behavioral and cognitive repertoire is habitual and results from sustained experience. We will also analyze the mechanisms that promote and modulate transmitter switching. Although it is clear that neurotransmitter switching is activity- dependent, the features of activity that are necessary to achieve switching remain unknown. In the future this knowledge may have clinical utility for driving or preventing transmitter switching in patients. The immediate goals of this research are to test specific hypotheses about the effect of activity in generating a novel form of plasticity that involves changes in transmitter identity in the adult mammalian brain. The long- term goals are to understand the role of neurotransmitter switching in regulating behaviors.

项目摘要摘要： 我们的看法，行为，情感，记忆和智力取决于适当的综合和 大脑中特定的神经递质的释放。发射机身份最初是由遗传确定的 程序。人们认为发射器一生都是固定和不变的，并且 神经系统主要包括突触的强度和数量。我们发现 持续感觉刺激的自发性电活动和自然变化的实验性扰动 例如环境光或气味使发育中的脊髓和大脑中的发射机身份重新定位 神经系统，导致突触后发射器受体规范的变化和变化 动物行为。令人惊讶的是，我们发现成人发射器开关和受体匹配也发生 哺乳动物大脑响应持续的感觉刺激，并可以调节行为。这些发现 与发射器恒定器的一般观点形成鲜明对比，并确定另一种紧张的方式 系统适应环境。 在这里，我们描述了实验，以确定单个诱导多少发射器开关 环境刺激以及有多少大脑区域受到影响。越来越了解 大脑是一个广泛联系的网络，单个扰动改变了整个大脑的活动。这很重要 解决此问题以更好地理解行为变化的基础 持续的刺激是我们行为的主要决定因素。我们行为和认知的主要部分 曲目是习惯性的，是持续经验的结果。我们还将分析机制 促进和调节发射机切换。尽管很明显，神经递质切换是活性 - 取决于实现开关所需的活动特征仍然未知。将来这个 知识可能具有临床实用性，可驾驶或预防患者的发射机切换。 这项研究的直接目标是检验有关活动在产生A的影响的特定假设 新颖的可塑性形式，涉及成年哺乳动物大脑中发射机身份的变化。长期 术语目标是了解神经递质切换在调节行为中的作用。