Basal Ganglia Activity Timing Underlying Habitual Behavior

习惯行为背后的基底神经节活动时间

• 批准号: 1557987
• 负责人: Kyle Smith
• 金额: $ 109.34万
• 依托单位: Dartmouth College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557987&HistoricalAwards=false
• 关键词: Basal; Ganglia; Activity; Timing; Underlying

Habits are a part of all animal life. Despite their ubiquity, it remains poorly understood how habits are formed and maintained in the brain. This research project will study how habits are represented in brain activity and how changing that activity can change habits. Science generally lacks an understanding of how fluctuating patterns of brain activity control behaviors like habits because, until recently, tools were not available to manipulate those brain patterns. Using cutting-edge techniques to do so, this work tests a central hypothesis that habits are controlled by the timing of brain activity related to when a habit is initiated and executed. Specifically, prior studies have uncovered a burst of brain activity as a behavior starts that correlates with how habitual the behavior is. This research evaluates how this pattern arises in the brain and whether it controls how habitual a behavior is by using tools to both monitor and manipulate the brain at the sub-second time-scale. Results will provide a rich understanding of how habits arise out of precisely timed bursts of brain activity. As part of this project, the cutting-edge research techniques are taught to undergraduate neuroscience students, which is a vital but lacking ingredient in their education. These techniques, and the brain basis of habits in general, also are taught to grade-schools and the public through outreach activities to convey progress science is making on understanding habits. Underrepresented individuals participate in all aspects of the research and outreach.In the brain, the dorsolateral striatum (DLS) and its dopamine input from the substantia nigra have long been implicated in habits. Neural recording studies have uncovered an activity pattern in these areas that characterizes habits, which involves a spiking burst at the start of behavior and diminished spiking mid-behavior. These dynamics suggest that it is the timing of brain activity that helps dictate whether or not a learned behavior occurs habitually. To test this, rats are exposed to lever-pressing and maze-running tasks that provide a screen of behavioral measures for habits. Activity in the DLS is recorded using electrodes as animals form habits and then modify them. Using optogenetics, in which DLS activity can be manipulated using pulses of light, the strength of the DLS activity is manipulated and consequences on habitual behavior and ongoing DLS dynamics assessed. The first and second objectives are to test if the strength of DLS activity at the start of a behavior is sufficient and necessary for that behavior to be expressed as a habit and for habit-related DLS activity to be maintained over time. The third objective is to test if start-related activity of dopamine input to the DLS is also critical for habits and for the start-related DLS activity that represents habits. Collectively, this work answers a long-standing question of how step-to-step fluctuations in DLS activity guide a behavior towards habitual expression and will merge isolated behavioral and neuroscience approaches to do so.

习惯是所有动物生活的一部分。 尽管它们无处不在，但人们对习惯如何在大脑中形成和维持仍然知之甚少。 这个研究项目将研究习惯如何在大脑活动中表现出来，以及改变这种活动如何改变习惯。 科学通常缺乏对大脑活动波动模式如何控制习惯等行为的理解，因为直到最近，还没有工具来操纵这些大脑模式。 这项工作使用尖端技术来做到这一点，测试了一个中心假设，即习惯是由与习惯开始和执行有关的大脑活动的时间控制的。 具体来说，先前的研究已经发现，当一种行为开始时，大脑活动的爆发与该行为的习惯程度有关。 这项研究评估了这种模式是如何在大脑中产生的，以及它是否通过使用工具在亚秒的时间尺度上监控和操纵大脑来控制行为的习惯程度。 研究结果将提供一个丰富的理解习惯是如何从精确定时的大脑活动爆发中产生的。 作为该项目的一部分，尖端研究技术被教授给神经科学本科生，这是他们教育中重要但缺乏的成分。 这些技术，以及习惯的大脑基础，也通过推广活动教授给小学和公众，以传达科学在理解习惯方面的进展。 在大脑中，背外侧纹状体（DLS）及其来自黑质的多巴胺输入长期以来与习惯有关。 神经记录研究揭示了这些区域的活动模式，这些活动模式是习惯的特征，包括行为开始时的尖峰爆发和行为中期的尖峰减少。 这些动态表明，正是大脑活动的时间有助于决定一种习得行为是否习惯性地发生。 为了验证这一点，老鼠被暴露在压力和迷宫运行任务，提供了一个屏幕的行为措施的习惯。 DLS中的活动是使用电极记录的，因为动物形成习惯，然后修改它们。 使用光遗传学，其中可以使用光脉冲操纵DLS活性，操纵DLS活性的强度，并评估对习惯性行为和正在进行的DLS动力学的影响。 第一个和第二个目标是测试在行为开始时DLS活性的强度是否足够并且对于该行为被表达为习惯以及对于习惯相关的DLS活性是否随时间保持是必要的。 第三个目标是测试是否启动相关的活动多巴胺输入到DLS也是至关重要的习惯和启动相关的DLS活动，代表习惯。 总的来说，这项工作回答了一个长期存在的问题，即DLS活动的逐步波动如何引导行为走向习惯性表达，并将合并孤立的行为和神经科学方法来实现这一目标。