How do Amine Neurons Work?

胺神经元如何工作？

基本信息

批准号：
8901200
负责人：
Edward A Kravitz
金额：
$ 32.21万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8901200
关键词：
Address Afferent Neurons Aggressive behavior Amines Animals Area Arousal Attention deficit hyperactivity disorder Behavior Behavioral Biological Models Brain Brain Stem Cell Nucleus Complex Courtship Databases Disease Dopamine Drosophila genus Drosophila melanogaster Drug Addiction Drug abuse Enhancers Functional disorder Generations Genetic Green Fluorescent Proteins Health Human Learning Libraries Life Literature Locomotion Membrane Memory Mental disorders Methods Mood Disorders Morphology Motivation Motor Nervous system structure Neurons Norepinephrine Nuclear Parkinson Disease Pathology Pattern Physiological Play Population Population Heterogeneity Procedures Process Property Rewards Risk-Taking Role Schizophrenia Serotonin Site Sleep Social Environment Stress Synapses System Time Work behavior test combinatorial dopaminergic neuron feeding fly genetic approach motor disorder nervous system disorder receptor recombinase response stress related disorder trait

项目摘要

DESCRIPTION (provided by applicant): Amine-containing neurons are found in relatively small numbers in specific nuclei deep within the brainstem in essentially all vertebrate species, including humans. Despite their limited numbers, amine effects on behavior are profound as their neuronal processes ramify widely throughout the nervous system. Dysfunctioning of amine neuron systems has been implicated in the pathology of many psychiatric and neurological diseases. Included are motor system disorders like Parkinson's Disease in which subsets of the dopamine neurons selectively die, and psychiatric disorders including mood disorders, schizophrenia, attention-deficit hyperactivity disorder and drug abuse in which the amines dopamine, serotonin and norepinephrine all have been directly implicated. Arousal, reward, learning and memory, risk taking behavior, aggression and stress related behavioral and physiological responses are some of the multitude of essential human behaviors in which amine neurons have been suggested to play key roles. With likely roles in so many central aspects of human behavior, it is no wonder that a huge literature has grown up on amine neuron systems and how they function. Originally thought to be fairly homogeneous populations of neurons found in selective CNS nuclear regions, continuing study has revealed that these systems instead are very heterogeneous populations of neurons in terms of their function and their morphology, even within single brainstem nuclei. The most challenging part of understanding these systems now is to understand how they coordinate and/or organize the many behavioral processes they seem concerned with. A difficulty in addressing such questions in higher vertebrate nervous systems is that even though the numbers of amine neurons involved are relatively small compared to the total numbers of neurons in the brain, it is highly unlikely that one will find the same neuron more than once to explore its function in detail. Recently developed methods in other model systems, however, allow targeting and manipulation of single "identified" amine neurons. These experimental approaches are the farthest advanced in fruit flies (Drosophila melanogaster) where powerful genetic methods allow identification and manipulation of single neurons concerned with behavior. As in vertebrate systems, amines have been shown to be intimately involved in many essential aspects of behavior in fruit flies, including motivation and reward, locomotion and feeding, learning and memory, and courtship and aggression. The studies proposed here have three Specific Aims concerned with bringing the study of how amine neurons work in fruit flies to an identified single neuron level. They are: Aim 1: Use of a combinatorial genetic approach to identify small subsets of amine neurons; Aim 2: The behavioral consequences of altering the functional properties of single amine-containing neurons; and Aim 3: Analysis of the circuitry associated with single amine neurons. Studies at these levels of detail are not possible in other species at the present time.

描述（由申请人提供）：在基本上所有脊椎动物（包括人类）的脑干深处的特定细胞核中发现相对少量的含胺神经元。尽管数量有限，但胺对行为的影响是深远的，因为它们的神经元过程广泛分布在整个神经系统中。胺神经元系统的功能障碍与许多精神和神经疾病的病理有关。其中包括运动系统疾病，如帕金森病，其中多巴胺神经元的子集选择性死亡，以及精神疾病，包括情绪障碍、精神分裂症、注意力缺陷多动障碍和药物滥用，其中多巴胺、血清素和去甲肾上腺素都与胺类物质直接相关。唤醒、奖励、学习和记忆、冒险行为、攻击性和压力相关的行为和生理反应是众多基本人类行为中的一些，胺神经元被认为在其中发挥着关键作用。由于胺神经元可能在人类行为的许多核心方面发挥作用，因此关于胺神经元系统及其功能的大量文献也就不足为奇了。最初被认为是在选择性中枢神经系统核区域中发现的相当同质的神经元群体，持续的研究表明，这些系统在功能和形态方面是非常异质的神经元群体，即使在单个脑干核内也是如此。现在理解这些系统最具挑战性的部分是理解它们如何协调和/或组织它们似乎关心的许多行为过程。在高等脊椎动物神经系统中解决此类问题的一个困难在于，尽管所涉及的胺神经元的数量与大脑中神经元的总数相比相对较小，但人们不太可能多次找到同一个神经元来进行识别。详细探讨其功能。然而，最近在其他模型系统中开发的方法允许靶向和操纵单个“识别的”胺神经元。这些实验方法在果蝇（Drosophila melanogaster）中是最先进的，其中强大的遗传方法允许识别和操纵与行为有关的单个神经元。与脊椎动物系统一样，胺已被证明与果蝇行为的许多基本方面密切相关，包括动机和奖励、运动和进食、学习和记忆、求偶和攻击。这里提出的研究有三个具体目标，涉及将胺神经元如何在果蝇中发挥作用的研究提升到已确定的单个神经元水平。它们是：目标 1：使用组合遗传方法来识别胺神经元的小子集；目标 2：改变单个含胺神经元功能特性的行为后果；目标 3：分析与单个胺神经元相关的电路。目前在其他物种中不可能进行如此详细的研究。