MCA: Arbitration between cortical and subcortical control of behavior

在理解包括人类在内的动物如何使用感官信息来指导行动方面，科学已经取得了重大进展。包括大脑皮层在内的高级大脑区域参与了证据的积累和决策的做出。但我们日常的许多行为都是由对感官刺激的无意识、自动或本能反应控制的。这些反应可以单独通过皮质下感觉脑区来完成。这项研究将解决关键问题，即这两种类型的感觉驱动行为是如何相互作用的。特别是，当这两种机制冲突时，大脑中的什么过程决定了更刻意的皮质反应或更自动的皮质下反应将占上风？这项研究将利用这样一个事实，即小鼠的一些视觉行为需要皮质处理，而另一些则不需要。通过创建一项使这两种行为发生冲突的新任务，研究人员将观察老鼠如何解决冲突，并确定控制仲裁的大脑机制。这个简单的案例涉及更广泛的问题，比如有意识的、有意的选择如何塑造或超越隐含的或与生俱来的行为驱动，以及压力或疲劳等因素如何影响皮质和皮质下之间的力量平衡。作为职业生涯中期促进奖，该项目还有一个重要的额外目标，即通过跨学科合作，为一名成熟的研究调查员提供高级技术培训，从而促进战略性劳动力发展，扩大对STEM的参与，并使研究趋同。该项目还将推动研究人员通过教育和研究活动促进科学的严谨性、稳健性和重复性的工作。在啮齿类动物中，一些视觉行为依赖于初级视觉皮质(V1)的完整功能，包括辨别格栅斑块中条纹的方向。其他视觉行为不依赖于大脑皮层，包括报告格栅贴片的位置。本研究将训练行为自由的小鼠报告两个同时呈现的光栅刺激中的哪一个具有靶向性，并分别训练它们报告两个同时呈现的光栅刺激中的哪个具有较高的对比度。他们将使用光基因沉默来确认V1是方位辨别任务所必需的，但不是对比度辨别任务所必需的。然后，当对比线索支持相同的选择、中立或冲突时，他们将挑战老鼠执行方位辨别任务。研究人员预计，小鼠将能够学会超越皮质下驱动的显著反应，并选择正确的定向目标，即使它们不那么显著。但他们预计，这场冲突将导致错误大幅增加。他们将使用基于机器学习的姿势估计来详细分析定向行为反应，并对潜在的决策进行建模。最后，他们将在上丘的所有层进行双边记录，以观察相互竞争的视觉目标在大脑皮质赢与输的行为控制竞争中争夺运动控制的动态。这项工作将建立一个新的模型系统，用于解剖神经电路和计算算法，通过这些系统，皮质处理对大脑皮层独立的感觉引导行为产生影响。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Science has made major strides in understanding how animals including humans use sensory information to guide actions. Higher brain areas, including cerebral cortex, are involved in accumulating evidence and triggering decisions. But much of our every-day behavior is controlled by unconscious, automatic, or instinctive responses to sensory stimuli. Those responses can be accomplished by sub-cortical sensory brain areas alone. This study will address the crucial question of how these two types of sensory-driven behavior interact. In particular, when these two mechanisms conflict, what processes in the brain determine whether the more deliberate, cortical, or the more automatic, sub-cortical, response will prevail? This study will leverage the fact that some visual behaviors of mice require cortical processing, while others do not. By creating a novel task in which these two behaviors come into conflict, the researchers will observe how mice resolve the conflict, and determine what brain mechanisms underlie the arbitration for control. This simple case relates to broader questions about how conscious, intentional choices shape or override implicit or innate behavioral drives, and how factors like stress or fatigue affect the balance of power between cortex and subcortex. As a Mid-Career Advancement award, the project has the important additional objective of providing advanced technical training to an established research investigator through an interdisciplinary collaboration, thus contributing to strategic workforce development, broadening participation in STEM, and enabling convergence research. The project will also further the investigator’s work on promoting rigor, robustness and reproducibility of science through educational and research initiatives.In rodents, some visual behaviors depend on the intact function of primary visual cortex (V1), including discriminating the orientation of stripes in a grating patch. Other visual behaviors are cortex-independent, including reporting the location of a grating patch. This study will train freely behaving mice to report which of two simultaneously presented grating stimuli has a target orientation, and separately train them to report which of two simultaneously presented grating stimuli has higher contrast. They will use optogenetic silencing to confirm that V1 is required for the orientation discrimination task, but not the contrast discrimination task. Then they will challenge the mice to perform the orientation discrimination task while the contrast cue either supports the same choice, is neutral, or is in conflict. The researchers expect that mice will be able to learn to override subcortically driven salience responses, and choose correct orientation targets even when they are less salient. But they expect that this conflict will induce a significant increase in errors. They will use machine-learning-based pose estimation to analyze in detail the orienting behavioral responses and model the underlying decision-making. Finally, they will record bilaterally in all layers of the superior colliculus to observe the dynamics with which the competing visual targets vie for determination of motor control, in trials in which cortex wins versus loses the contest for control of behavior. This work will establish a new model system for dissecting the neural circuitry and computational algorithms through which cortical processing exerts influence over cortex-independent sensory-guided behaviors.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.