Mechanisms for internally and externally guided sensorimotor learning

内部和外部引导的感觉运动学习机制

• 批准号: 9217348
• 负责人: Richard D Mooney
• 金额: $ 43万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9217348
• 关键词: Acute; Address; Adolescent; Adult; Affect; Auditory; Basal Ganglia; Basal Ganglia Diseases; Behavior; Behavior Control; Behavioral; Brain; Calcium; Cells; Complex; Cues; Disease; Dopamine; Dopamine D1 Receptor; Dopamine Receptor; Functional disorder; Genetic; Health; Human; Image; Learning; Light; Measures; Mediating; Methods; Microdialysis; Modeling; Monitor; Motor; Motor Skills; Movement Disorders; Mutation; Neural Pathways; Neurons; Noise; Output; Pathology; Performance; Play; Psychological reinforcement; Punishment; Recovery; Research; Resolution; Rewards; Role; Signal Transduction; Songbirds; Source; Speech; Speech Pathology; Testing; Ventral Tegmental Area; auditory feedback; genetic manipulation; imaging genetics; innovation; motor learning; nervous system disorder; neural circuit; neuromechanism; novel; optogenetics; postsynaptic; reinforced behavior; relating to nervous system; response; vocal learning; vocalization

Neurons in the ventral tegmental area (VTA) play a key role in motor learning, and neurological diseases that affect VTA neurons or their targets in the basal ganglia (BG) severely disrupt behavior. Notably, much of our understanding of how the VTA functions in motor learning has relied on paradigms that employ external reward or punishment and involve relatively slow and simple behaviors, such as lever pressing or licking. In contrast, many of our most complex and valued behaviors, such as speech and musical expression, can be learned without external reinforcement, suggesting that their learning is internally reinforced. Further, internally reinforced behaviors such as speech or musicianship require highly complex and rapid motor sequences and are more readily acquired during juvenile sensitive periods. How the VTA interacts with the BG to mediate complex forms of internally and externally reinforced auditory-motor learning remains unknown. Here we propose to identify how the VTA and BG interact to mediate different forms of auditory-motor learning using a novel combination of intersectional genetic methods to selectively ablate VTA neurons, microdialysis, calcium imaging and optogenetic manipulation of VTA terminals and BG neurons combined with rapid and temporally precise behavioral manipulations. These approaches will be used to test the hypothesis that the VTA functions as a “critic” that evaluates auditory feedback and instructively modifies BG premotor activity, which in turn drives internally and externally reinforced auditory- motor learning. Resolving how VTA-BG circuits mediate these forms of learning are critical issues for understanding motor plasticity in health and disease. In fact, speech pathologies typify various diseases that affect VTA-BG circuitry, while mutations that disrupt dopamine-mediated signaling in the BG also impair vocal learning. Therefore, the proposed research can shed light on the neural circuit mechanisms that enable complex internally and externally reinforced behavioral learning while also revealing how dysfunction in these circuits interferes with the learning and execution of communicative behaviors.

腹侧盖区域（VTA）的神经元在运动学习中起关键作用，神经疾病 这会影响VTA神经元或基底神经节（BG）的靶标严重破坏行为。值得注意的是 我们对VTA在运动学习中的功能的理解已依赖于采用的范例 外部奖励或惩罚，涉及相对缓慢而简单的行为，例如杠杆紧迫或 舔。相比之下，我们许多最复杂，最有价值的行为，例如言语和音乐 表达，可以在没有外部强化的情况下学习，表明他们的学习是内部的 加强。此外，内部加强的行为，例如言语或音乐才能需要高度复杂 和快速运动序列，在少年敏感时期更容易获得。 VTA如何 与BG相互作用以介导内部和外部增强的听觉运动的复杂形式 学习仍然未知。在这里，我们建议确定VTA和BG如何相互作用以介导不同 使用交叉遗传学方法的新型组合以选择性地学习听觉运动的形式 VTA末端和BG的植物VTA神经元，微透析，钙成像和光遗传操作 神经元结合了快速且暂时精确的行为操纵。这些方法将是 用于检验VTA作为评估听觉反馈和的“评论家”的假设 主导性修改BG前运动活动，这又在内部和外部增强的听觉驱动 运动学习。解决VTA-BG电路如何调节这些形式的学习形式是关键问题 了解健康和疾病中的运动可塑性。实际上，语音病理典型的各种疾病 影响VTA-BG电路，而破坏多巴胺介导的信号传导的突变也损害 声带学习。因此，拟议的研究可以阐明神经回路机制 在内部和外部增强的行为学习中启用复合物，同时还揭示了功能障碍 在这些电路中，会干扰传达行为的学习和执行。