Circuit and neurotransmitter mechanisms underlying neural and behavioral variabil

神经和行为变异背后的电路和神经递质机制

• 批准号: 7163326
• 负责人: Allison Jane Doupe
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163326
• 关键词: age difference; basal ganglia; dopamine; neural information processing; neurotransmitters; norepinephrine; songbirds; vocalization

In songbirds, a discrete neural circuit is devoted to the learning and production of a stereotyped vocal motor behavior, song, providing a useful model for studying brain mechanisms of behavior, with strong relevance to human speech learning. In particular, a specialized 'cortical'-basal ganglia circuit known as the anterior forebrain pathway (AFP) is crucial for song learning and plasticity throughout life. Recent evidence from our lab and others has revealed that the AFP provides a source of variability potentially important for learning to the motor circuit. In addition, we have found that the outflow nucleus of the AFP, 'LMAN', switches from bursty, highly variable firing when birds sing alone, to more reproducible firing when birds sing to a female, suggesting that social cues could be important in the control of variability. The two social states of LMAN activity are associated with high and low variability song, respectively. Here we propose to further investigate the function of AFP variability by examining and then manipulating the circuit and neurotransmitter mechanisms that give rise to it. We will record chronically from cells in the basal ganglia inputs to LMAN as well as from LMAN neurons, to study where the social context-dependent variability of firing emerges and how it travels across this circuit. We will also measure how correlated LMAN firing is across neurons, to assess how variability may be 'read out' to the motor pathways, and how it relates to behavior (Aim 1). We will then alter the levels of the neuromodulators norepinephrine (NE) and dopamine (DA) both in adults (Aim 2) and in juveniles in late sensorimotor learning (Aim 3), and examine the effects on AFP activity and on song, to test the hypothesis that these neurotransmitters regulate neural and consequently behavioral variability. The song system provides a tractable model for studying the mechanisms by which social and other environmental cues act on the nervous system and ultimately affect behavioral output, both normally and in disease. Understanding these mechanisms has the potential to provide insights into the many neuropsychiatric disorders that have their locus in cortical-basal ganglia circuits.

在鸣禽中，一个离散的神经回路专门用于学习和产生一个定型的发声运动 行为，歌曲，为研究行为的大脑机制提供了一个有用的模型，与 人类语言学习特别是，一个专门的'皮质'-基底神经节电路称为前 前脑通路（AFP）是至关重要的歌曲学习和可塑性在整个生命。我们最近的证据显示， 实验室和其他人已经揭示，AFP提供了一个可变性的来源，对于学习 电机电路。此外，我们还发现AFP的流出核“LMAN”从 当鸟类单独唱歌时，爆发性的，高度可变的放电，当鸟类对雌性唱歌时， 这表明社会线索在控制变异性方面可能很重要。LMAN的两种社会状态 活动分别与高和低可变性歌曲相关。在此，我们建议进一步调查 通过检查并操纵回路和神经递质， 我们将长期记录基底神经节细胞对LMAN的输入， 以及LMAN神经元，以研究放电的社会背景依赖性变化出现的地方， 它是如何通过这条线路的我们还将测量LMAN放电在神经元中的相关性， 评估变异性如何被“读出”到运动通路，以及它如何与行为相关（目标1）。我们 然后会改变成年人的神经调节剂去甲肾上腺素（NE）和多巴胺（DA）的水平（Aim 2)和青少年在后期感觉运动学习（目的3），并检查对AFP活性和 歌曲，以测试假设，这些神经递质调节神经，从而行为 可变性歌曲系统提供了一个易于处理的模型，用于研究社会和 其他环境线索作用于神经系统，并最终影响行为输出，这两个正常 和疾病。了解这些机制有可能提供对许多 神经精神障碍，其所在地在皮质-基底神经节回路中。