Lagging or Leading? Linking Substantia Nigra Activity to Spontaneous Motor Sequences

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• 批准号: 9146703
• 负责人: Ryan Prescott Adams
• 金额: $ 56.76万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-22 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9146703
• 关键词: Animals; Basal Ganglia; Behavior; Behavioral; Brain; Cell Nucleus; Complex; Cues; Disease; Environment; Food; Goals; Health; Instinct; Laboratories; Learning; Light; Link; Mental disorders; Methods; Motor; Movement; Neurons; Odors; Output; Pattern; Play; Population; Psychological reinforcement; Research; Specific qualifier value; Statistical Models; Stereotyping; Substantia nigra structure; System; Technology; Testing; Thalamic structure; Training; Vision; Work; approach avoidance behavior; flexibility; learned behavior; nervous system disorder; neural correlate; new technology; novel; optogenetics; relating to nervous system; response

 DESCRIPTION (provided by applicant): Behaviors are sequences of actions that are executed in the proper order and correct setting to achieve a goal. Action sequences and their association with the specific environmental contexts in which they are beneficial can be hardwired, as in the case of innate behaviors, or learned and flexible, as in the case of adaptive responses to changing surroundings. The basal ganglia, a complex set of phylogenetically ancient subcortical nuclei, collect sensorimotor information from across the cortical mantle and project via output nuclei to thalamic structures that regulate action; this circuit organization suggests that the basal ganglia may play key roles in modulating ongoing patterns of action. Consistent with this possibility, neurological and psychiatric diseases that disrupt basal ganglia function also disrupt action selection, sequencing and execution. Furthermore, neural correlates have been identified within the basal ganglia that predict, accompany and lag different features of behavior. However, three key questions remain open about the relationship between basal ganglia activity and behavior. First, it is unclear whether the basal ganglia primarily encode behavioral sequences, the action components of behavioral sequences, or both. Second, because of the temporal diversity of task-related activity observed in the basal ganglia, it is not clear whether activity in specific populations of neurons is causal for behavior. Finally, because most research into basal ganglia function involves overtraining in operant tasks, it is not clear what the core principles of action encoding are that govern basal ganglia function during spontaneously generated patterns of behavior like exploration. Here we propose to take advantage of a novel 3D machine vision technology uses Baysean inference to classify spontaneous behavior on fast (e.g. neural) timescales to probe the causal relationships between neural activity in the basal ganglia and action. We will focus our analysis of the main output nucleus of the basal ganglia; the substantia nigra pars reticulate (SNpr). We will first seek to identify predictive neural correlates within the SNpr for action components and behavioral sequences by combining our behavioral analysis methods with dense electrical recordings, both during normal exploration and during the execution of innate approach and avoidance behaviors triggered by odor cues from foods, conspecifics and predators. We will then test the causal relationship between activity in these SPnr neurons and specific features of behavior by using closed- loop optogenetics to subtly alter global patterns of activity within SPnr neurons themselves. This work will shed light on the mechanisms used by the brain to create self-generated patterns of action, and yield important clues about how the links between neural activity and action are altered during disease.

 描述（由适用提供）：行为是以正确顺序执行并正确设置以实现目标的动作序列。动作序列及其与它们具有有益的特定环境环境的关联，就像天生的行为一样，或者学习和灵活，就像对改变周围环境的自适应响应一样。基底神经节是一组复杂的系统发育中古老的下皮质核，从皮质地幔和通过输出核项目中收集感官信息，并通过输出核向调节作用的丘脑结构收集。该电路组织建议基底神经节在调节正在进行的行动模式中起关键作用。与这种可能性一致，破坏基础神经节功能的神经和精神病疾病也破坏了行动选择，测序和执行。此外，在预测，参加和滞后行为的不同特征的基底神经节中已经确定了神经元相关性。但是，关于基底神经节活动和行为之间关系的三个关键问题仍然是持开放态度的。首先，目前尚不清楚基础神经节主要编码行为序列，行为序列的作用成分还是两者兼而有之。其次，由于在基底神经节中观察到与任务相关的活动的暂时多样性，所以不是 清除特定神经元群体中的活性是否对行为有灾难性。最后，由于大多数对基底神经节功能的研究都涉及在操作任务中过度训练，因此尚不清楚行动编码的核心原则是在赞助的行为模式（例如探索）中控制基础神经节功能。在这里，我们建议利用一种新颖的3D机器视觉技术利用Baysean推断来对快速（例如神经）时间表上的赞助行为进行分类，以探测基底神经节和动作中神经元活动之间的因果关系。我们将集中精力分析基底神经节的主要产量核。黑质Nigra pars网状（SNPR）。我们将首先寻求通过将我们的行为分析方法与密集的电记录相结合，无论是在正常探索期间还是在正常探索过程中，以及由食物，细节和掠食者的气味提示触发的行为和回避行为，从而确定SNPR中的预测性神经元相关性，以实现行动组件和行为序列。然后，我们将通过使用闭环光遗传学来巧妙地改变SPNR神经元本身内的全局活动模式，以测试这些SPNR神经元中活动与行为特定特征之间的因果关系。这项工作将阐明大脑为创建自我生成的作用模式的机制，并就疾病期间神经活动与动作之间的联系产生重要的群集。