Control of procedural learning by parallel cortico-basal ganglia pathways

描述（由申请人提供）：在哺乳动物大脑中连接皮质和基底神经节的循环回路介导各种类型的程序性学习，例如获得导致习惯性运动序列的行为技能。在刻板运动习惯的获得过程中，平行的皮质-基底神经节回路控制着不同但相关的功能：（1） 评估与目标相关的特定行为动作和（2）指导运动表现以选择适当的动作。关于程序学习机制的一个基本问题是：神经回路如何评估行为结果并使用这些评估来实现正确的行为目标？鸣禽的发声学习代表了一种程序性学习，其中通过反馈评估自我产生的发声，并逐步改进以实现对记忆的发声声音的模仿。这个过程需要大脑将当前发声行为的反馈与目标--发声声音的记忆--进行比较。我们已经发现，平行的CORE和SHELL皮质基底神经节通路控制鸣禽大脑中的目标导向与运动相关的发声学习方面，从而提供了一个强大的模型来研究导致刻板的运动习惯的程序性学习的神经机制。我们将研究平行的核心和外壳通路支持发声学习早期阶段的机制，作为皮质基底神经节回路如何介导“动作结果”评估的模型。拟议的实验将测试的想法，壳电路是一个主要网站的比较行为反馈的神经记忆的声音，而这种目标导向的学习的结果是必要的准确模仿的声音。我们将记录清醒行为鸣禽的SHELL回路中单个神经元的神经活动，因为它们积极参与学习，以测试如何根据行为反馈是否与声音的目标记忆相匹配来产生评价信号。我们还将改变幼年鸣禽的SHELL回路中的正常神经活动，以测试评估信号的中断是否会损害特定声音的学习。这些研究将阐明目标导向评价的机制，以及它们如何影响程序性学习的初始阶段。程序性学习及其神经基础的研究对于理解涉及刻板行为的各种障碍是必不可少的，包括帕金森病，亨廷顿病，强迫症，图雷特综合征，自闭症谱系障碍和雷特综合征。

DESCRIPTION (provided by applicant): Recurrent circuits linking the cortex and basal ganglia in the mammalian brain mediate various types of procedural learning, such as acquisition of behavioral skills resulting in a habitual sequence of movements. Parallel cortico-basal ganglia circuits control distinct but related functions during acquisition of stereotyped motor habits: (1) evaluating specific behavioral actions in relation to a goal and (2) guiding motor performance to select appropriate actions. A fundamental question with regard to mechanisms of procedural learning is: how do neural circuits evaluate behavioral outcomes and use those evaluations in order to achieve the correct behavioral goal? Vocal learning in songbirds represents a type of procedural learning in which self-produced vocalizations are evaluated via feedback and progressively refined to achieve an imitation of memorized vocal sounds. This process requires the brain to compare feedback of current vocal behavior to the goal - the memory of vocal sounds. We have discovered that parallel CORE and SHELL cortico-basal ganglia pathways control goal-oriented versus motor-related aspects of vocal learning in songbird brain, thus providing a powerful model to study neural mechanisms of procedural learning that lead to stereotyped motor habits. We will investigate mechanisms by which parallel CORE and SHELL pathways support early stages of vocal learning as a model for how cortico-basal ganglia circuits mediate "action-outcome" evaluations. The proposed experiments will test the idea that SHELL circuitry is a primary site of comparison of behavioral feedback to the neural memory of vocal sounds, and that the results of this goal-oriented learning are necessary for accurate imitation of vocal sounds. We will record neural activity of single neurons in SHELL circuits in awake behaving songbirds as they are actively engaged in learning in order to test how evaluative signals are generated depending on whether behavioral feedback matches the goal memory of vocal sounds. We will also alter normal neural activity in SHELL circuits in juvenile singing birds to test whether disruption of evaluative signals impairs learning of specific vocal sounds. These studies will elucidate mechanisms of goal-oriented evaluation and how they influence initial stages of procedural learning. Investigations of procedural learning and its neural substrate are essential for understanding a variety of disorders involving stereotypic behaviors, including Parkinson's disease, Huntington's disease, obsessive-compulsive disorders, Tourette syndrome, autism spectrum disorders, and Rett syndrome.