Control of procedural learning by parallel cortico-basal ganglia pathways

描述(申请人提供)：哺乳动物大脑中连接皮质和基底节的循环回路调节各种类型的程序性学习，例如获得导致习惯性动作序列的行为技能。在习得刻板的运动习惯过程中，平行的皮质-基底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，以及(2)指导运动表现以选择适当的动作。关于程序性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，在这种学习中，通过反馈对自己产生的发声进行评估，并逐步改进以实现对记忆的发声的模仿。这个过程需要大脑将当前发声行为的反馈与目标--发声记忆--进行比较。我们发现，在鸣禽大脑中，平行的核心和外壳皮质-基底节通路控制着发声学习的目标导向和运动相关方面，从而为研究导致刻板印象的运动习惯的程序性学习的神经机制提供了一个强有力的模型。我们将研究并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-基底节回路如何调节“行动-结果”评估的模型。拟议的实验将检验这样一种观点，即外壳电路是比较行为反馈与声音神经记忆的主要场所，并且这种目标导向学习的结果对于准确模拟声音是必要的。我们将记录清醒的鸣禽在积极学习时外壳电路中单个神经元的神经活动，以测试评估信号是如何根据行为反馈是否与发声的目标记忆匹配而产生的。我们还将改变幼年鸣禽外壳回路中正常的神经活动，以测试评估信号的中断是否会损害对特定声音的学习。这些研究将阐明目标导向评估的机制以及它们如何影响程序性学习的初始阶段。对程序性学习及其神经基础的研究对于理解包括帕金森病、亨廷顿病、强迫症、抽动症、自闭症谱系障碍和雷特综合征在内的各种刻板行为障碍是至关重要的。

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.