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: 8141345
• 负责人: STEPHEN G LISBERGER
• 金额: $ 18.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8141345
• 关键词: Circuit; neurotransmitter; mechanisms; underlying; neural

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，一个离散的神经电路致力于学习和生产刻板印象的声带 行为，歌曲，为研究行为的大脑机制提供了有用的模型，与 人类的言语学习。特别是，专门的“皮质”基形神经节电路被称为前 前脑道路（AFP）对于一生中的歌曲学习和可塑性至关重要。我们的最新证据 实验室和其他人透露，法新社提供了一种可变性的来源，这对于学习可能很重要 电机电路。此外，我们发现AFP“ LMAN”的流出核从 鸟儿单独唱歌时爆发，高度可变的射击，当鸟类向女性唱歌时更可重复的射击， 表明社会提示对于控制变异性可能很重要。 Lman的两个社会状态 活动分别与高和低变异性歌曲有关。在这里，我们建议进一步调查 通过检查和操纵电路和神经递质，AFP变异性的功能 引起它的机制。我们将从基底神经节输入到Lman的细胞长期记录到Lman 以及从LMAN神经元开始研究社会背景依赖解雇的可变性的地方 它如何在该电路上行驶。我们还将衡量神经元跨神经元的关联性射击与 评估如何将变异性“读取”到电路通路，以及它与行为的关系（AIM 1）。我们 然后将改变成人的神经调节剂去甲肾上腺素（NE）和多巴胺（DA）的水平（AIM 2）和少年在后期感觉运动学习中（AIM 3），并检查对AFP活动的影响 歌曲，以测试这些神经递质调节神经并因此行为的假设 可变性。歌曲系统提供了一个可易于研究的模型，用于研究社交和社交机制 其他环境提示对神经系统作用，最终影响行为输出 和疾病。了解这些机制有潜力为许多人提供见解 神经精神疾病在皮质基质神经节电路中具有其基因障碍。