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，离散的神经回路致力于学习和产生刻板的发声运动 行为，歌曲，为研究大脑行为机制提供了一个有用的模型，与 人类语音学习。特别是，一个专门的“皮质”-基底神经节回路，称为前部 前脑通路（AFP）对于终生的歌曲学习和可塑性至关重要。我们的最新证据 实验室和其他人已经揭示，AFP 提供了一个可变性来源，对于学习 电机电路。此外，我们发现 AFP 的流出核“LMAN”从 当鸟类单独唱歌时，会出现突发性、高度可变的放电，而当鸟类向雌鸟唱歌时，放电会更加重复， 表明社会线索对于控制变异性可能很重要。 LMAN的两种社会状态 活动分别与高变异性和低变异性歌曲相关。在此我们建议进一步调查 通过检查然后操纵电路和神经递质来了解 AFP 变异性的功能 产生它的机制。我们将长期记录基底神经节细胞对 LMAN 的输入： 以及来自 LMAN 神经元的研究，以研究放电的社会环境依赖性变异性在何处出现，以及 它如何穿过这条电路。我们还将测量 LMAN 放电在神经元之间的相关性，以 评估如何将变异性“读出”到运动通路，以及它与行为的关系（目标 1）。我们 然后会改变成人神经调节剂去甲肾上腺素 (NE) 和多巴胺 (DA) 的水平（目标 2) 和青少年晚期感觉运动学习（目标 3），并检查对 AFP 活动和 歌曲，以检验这些神经递质调节神经进而行为的假设 可变性。歌曲系统为研究社会和文化的机制提供了一个易于处理的模型。 其他环境因素作用于神经系统并最终影响行为输出，通常都是如此 以及在疾病中。了解这些机制有可能提供对许多方面的见解 位于皮质-基底神经节回路的神经精神疾病。