MCA: Arbitration between cortical and subcortical control of behavior

科学在理解包括人类在内的动物如何利用感官信息指导行动方面取得了重大进展。包括大脑皮层在内的高级大脑区域负责积累证据和触发决策。但是，我们的日常行为大多是由对感官刺激的无意识的、自动的或本能的反应控制的。这些反应可以由皮层下感觉脑区单独完成。这项研究将解决这两种类型的感觉驱动行为如何相互作用的关键问题。特别是，当这两种机制发生冲突时，大脑中的哪些过程决定了更深思熟虑的皮层反应，还是更自动的皮层下反应会占上风？这项研究将利用这样一个事实，即老鼠的一些视觉行为需要皮层处理，而另一些则不需要。通过创造一个让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到更广泛的问题：有意识的、有意的选择如何塑造或超越内隐的或先天的行为驱动，以及压力或疲劳等因素如何影响皮层和皮层下的权力平衡。作为一项中期职业发展奖，该项目还有一个重要的额外目标，即通过跨学科合作，为成熟的研究人员提供先进的技术培训，从而为战略劳动力发展做出贡献，扩大STEM的参与，并实现融合研究。该项目还将通过教育和研究活动进一步促进研究者在促进科学的严谨性、稳健性和可重复性方面的工作。在啮齿类动物中，一些视觉行为依赖于初级视觉皮层（V1）的完整功能，包括在光栅斑块中识别条纹的方向。其他视觉行为是独立于皮质的，包括报告光栅补丁的位置。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哪一个具有目标取向，并单独训练它们报告两个同时呈现的光栅刺激中哪一个具有更高的对比度。他们将使用光遗传沉默来证实V1是取向区分任务所需要的，而不是对比区分任务所需要的。然后，他们将挑战小鼠执行定向辨别任务，而对比线索要么支持相同的选择，要么是中立的，要么是冲突的。研究人员期望小鼠能够学会超越皮层下驱动的显著性反应，并选择正确的定向目标，即使它们不那么显著。但他们预计这种冲突将导致错误的显著增加。他们将使用基于机器学习的姿态估计来详细分析定向行为反应，并为潜在的决策建模。最后，他们将在双侧上丘的所有层进行记录，以观察竞争的视觉目标争夺运动控制的动态，在皮层赢得或失去对行为控制的竞争的试验中。这项工作将建立一个新的模型系统来解剖神经回路和计算算法，通过这些神经回路和计算算法，皮层处理对皮层独立的感觉引导行为施加影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.