Basal Ganglia Activity Timing Underlying Habitual Behavior

习惯是所有动物生活的一部分。尽管习惯无处不在，但人们对它们是如何在大脑中形成和维持的仍然知之甚少。这个研究项目将研究习惯如何在大脑活动中表现出来，以及改变大脑活动如何改变习惯。科学界普遍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，还没有工具可以操纵这些大脑模式。利用尖端技术，这项工作验证了一个中心假设，即习惯是由大脑活动的时间控制的，而大脑活动与习惯的产生和执行时间有关。具体来说，之前的研究已经发现，当一种行为开始时，大脑活动的爆发与这种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在亚秒时间尺度上监测和操纵大脑的工具来控制习惯性行为的程度。研究结果将提供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，向神经科学本科学生教授前沿研究技术，这是他们教育中至关重要但缺乏的要素。这些技巧，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取得的进展。代表性不足的个人参与研究和推广的各个方面。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一直与习惯有关。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弱。这些动态表明，大脑活动的时间有助于决定学习行为是否习惯性地发生。为了验证这一点，实验鼠被暴露在按压杠杆和跑迷宫的任务中，这些任务为习惯提供了一系列行为测量。当动物形成习惯并加以改变时，DLS的活动被电极记录下来。利用光遗传学，DLS活动可以通过光脉冲来控制，DLS活动的强度可以被控制，对习惯行为和持续DLS动态的影响进行评估。第一个和第二个目标是测试一种行为开始时DLS活动的强度是否足够和必要，以使该行为表现为习惯，以及与习惯相关的DLS活动是否能长期维持。第三个目标是测试多巴胺输入到DLS的启动相关活动是否对习惯和代表习惯的启动相关DLS活动也至关重要。总的来说，这项工作回答了一个长期存在的问题，即DLS活动的逐级波动如何指导习惯性表达的行为，并将结合孤立的行为和神经科学方法来做到这一点。

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.