Dissecting the basal ganglia's contribution to sensorimotor learning and generalization

剖析基底神经节对感觉运动学习和泛化的贡献

• 批准号: 8835956
• 负责人: Lukas A. Hoffmann
• 金额: $ 4.27万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2016-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8835956
• 关键词: Address; Adolescent; Adult; Affect; Animal Model; Area; Auditory; Automobile Driving; Basal Ganglia; Basal Ganglia Diseases; Behavior; Behavior Control; Behavioral; Behavioral Paradigm; Biological Models; Birds; Brain; Cell Nucleus; Complex; Corpus striatum structure; Development; Disease; Dopamine; Exhibits; Finches; Functional disorder; Gestures; Goals; Human; Infant; Injury; Investigation; Knowledge; Learning; Lesion; Measurement; Mediating; Modeling; Modification; Motor; Motor output; Movement; Neurons; Neurosciences; Output; Parents; Pathology; Patients; Pattern; Play; Process; Production; Psychological Transfer; Psychological reinforcement; Rehabilitation therapy; Reporting; Research Proposals; Rewards; Role; Sensory; Series; Signal Transduction; Songbirds; Stroke; Symptoms; System; Testing; auditory feedback; base; behavior change; dopaminergic neuron; improved; innovation; learned behavior; learning ability; motor deficit; motor learning; nervous system disorder; neurophysiology; novel; public health relevance; relating to nervous system; response; vocal control; vocal learning; vocalization

DESCRIPTION (provided by applicant): Patients with basal ganglia disease or injury suffer from a wide range of motor deficits, including deficiencies in the ability to correct movement errors and learn new movements. Although we know that the basal ganglia is important for learning, we still know relatively little of how it contributes to motor plasticity, hindering the understanding and treatment of deficits after neurological disorders and stroke. In particular, it s not clear how it acts to guide learned adjustments of motor output in response to sensory error signals. It is also unclear whether it plays a major function in transferring learning to new contexts ("generalization"). Finally, although dopamine signaling has long been proposed as being important for learning, its role in learning and generalization remains poorly understood. The proposed project will leverage an animal model (the songbird) uniquely suited for addressing this knowledge gap. Bengalese finches exhibit a complex learned motor behavior (song) maintained via sensorimotor error correction. Their song consists of a series of rapidly produced vocal gestures, or "syllables", which they learn as juveniles from adult tutors, much as human infants learn to speak from parents. A network of interconnected nuclei known as the song system enables song learning and production. The basal ganglia nucleus Area X forms an integral part of this system and has many similarities and homologies to the human basal ganglia. Our lab has developed a novel behavioral paradigm to evoke adaptive vocal changes and generalization behavior in Bengalese finches by altering auditory feedback. This paradigm will allow us to pursue the long-term objective of understanding in detail the basal ganglia's and dopamine's role in learning and generalization. Our central hypothesis is that vocal learning is mediated by dopamine signaling in the basal ganglia and that change in basal ganglia firing patterns during learning underlie learned changes in song. This hypothesis will be tested through two Aims. In Aim 1, it will be determined how complete lesions of Area X, and selective lesions of the dopamine neurons projecting to Area X, affect learning ability. In Aim 2 Area X neurons will be recorded in singing birds while driving learning. Changes in Area X neural activity will be related to the changes in vocal output. Two aspects of learning will be investigated: adaptive modification of the specific gestures during which sensory errors occurred, and generalization of this learning to other gestures. Learning will be driven by altering auditory feedback on specific vocalizations within the song and observing how the bird changes both the altered and unaltered vocalizations to compensate. Together, these studies will yield a detailed characterization of the basal ganglia's role in motor learning.

描述（由申请人提供）：基底神经节疾病或损伤患者存在广泛的运动缺陷，包括纠正运动错误和学习新运动的能力不足。虽然我们知道基底神经节对学习很重要，但我们仍然对它如何有助于运动可塑性知之甚少，这阻碍了对神经系统疾病和中风后缺陷的理解和治疗。特别是，它是如何引导运动输出的学习调整以响应感觉错误信号的，目前还不清楚。也不清楚它是否在将学习转移到新的环境（“泛化”）中发挥主要作用。最后，虽然多巴胺信号一直被认为对学习很重要，但它在学习和泛化中的作用仍然知之甚少。 拟议的项目将利用一种动物模型（鸣禽）来填补这一知识空白。孟加拉雀表现出一种复杂的学习运动行为（歌曲），通过感觉运动错误纠正来维持。它们的歌声由一系列快速产生的声音手势或“音节”组成，它们在青少年时期从成年导师那里学习，就像人类婴儿从父母那里学习说话一样。一个被称为歌曲系统的相互连接的细胞核网络使歌曲学习和产生成为可能。基底神经节核X区形成了这个系统的一个组成部分，并与人类基底神经节有许多相似之处和同源性。我们的实验室已经开发出一种新的行为范式，通过改变听觉反馈来唤起孟加拉雀的适应性声音变化和泛化行为。这种范式将使我们能够追求详细了解基底神经节和多巴胺在学习和概括中的作用的长期目标。 我们的中心假设是，声乐学习是介导的多巴胺信号在基底神经节和基底神经节放电模式的变化，在学习过程中的基础学习的变化，歌曲。这一假设将通过两个目标进行检验。在目标1中，将确定X区的完全损伤以及投射到X区的多巴胺神经元的选择性损伤如何影响学习能力。在Aim 2中，X区神经元将在驾驶学习时记录在唱歌的鸟类中。X区神经活动的变化将与声音输出的变化相关。学习的两个方面将进行调查：自适应修改的具体手势，在此期间发生的感觉错误，并推广这种学习到其他手势。学习将通过改变歌曲中特定发声的听觉反馈来驱动，并观察鸟如何改变改变和未改变的发声来补偿。总之，这些研究将产生基底神经节在运动学习中的作用的详细描述。