Determining Fundamental Properties of Neurotransmitter Switching in Adult Mammals

项目摘要摘要： 我们的感知、行为、情感、记忆和智力依赖于适当的综合和 在大脑中释放特定的神经递质。传递者的身份最初是由基因建立的 程序。人们一直认为，发射器在整个生命过程中是固定和不变的，而且 神经系统在很大程度上由突触强度和数量的变化组成。我们发现， 自发性电活动的实验扰动和持续感觉刺激的自然变化 例如，环境光或气味在发育过程中重新指定脊髓和大脑中的递质身份 神经系统，导致突触后递质受体规格的匹配变化和 动物的行为。令人惊讶的是，我们发现在成人中也发生了递质转换和受体匹配 哺乳动物的大脑对持续的感觉刺激做出反应，并能调节行为。这些发现 与发射器恒定的一般观点形成鲜明对比，并确定另一种紧张的方式 系统能够适应环境的变化。 在这里，我们描述了确定由一个单一的 环境刺激以及有多少大脑区域受到影响。越来越多的人认识到， 大脑是一个广泛连接的网络，单一的干扰会改变整个大脑的活动。这很重要 要解决这一问题，以便更好地了解行为变化的基础 持续的刺激是我们行为的主要决定因素。我们的行为和认知的一个主要部分 曲目是习惯性的，是持续经验的结果。我们还将分析 促进和调节发射机切换。尽管很明显，神经递质的转换是一种活动- 根据具体情况，实现切换所需的活动特征仍不清楚。在未来，这个 这些知识可能对推动或防止患者的发射器切换具有临床实用价值。 这项研究的直接目标是测试关于活动在产生 一种新的可塑性形式，涉及成年哺乳动物大脑中递质身份的变化。长的- 学期目标是了解神经递质转换在调节行为中的作用。

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.