Cell-type-specific Connectivity of Brainstem Circuits Mediating the Cortical Control of Innate Reflexes

哺乳动物大脑的一个显著特征是新皮层的巨大扩张，这是一种遗传学上的现代结构。尽管我们对大脑皮层的感觉处理能力有着丰富的了解，但我们对大脑皮层如何影响行为，尤其是条件反射知之甚少。反射性行为，如逃避威胁，是一种先天的无意识运动行为，几乎是对外部刺激的瞬间反应，对动物的生存至关重要。虽然先天反射是由硬连线的皮层下结构（如脑干）介导的，但也可以由皮层调节，这取决于当时的条件和过去的经验。这种皮层对反射的调节代表了一种基本的进化适应，因为它允许生物体调整其反射行为，以应对动态变化的环境。一个最好的例子是视动反射（OKR）的自适应皮层控制，这是一种先天的眼球运动，当动物在环境中移动时，它可以稳定视网膜上的图像。OKR是高度可塑的;事实上，当其他眼反射受损时，它的振幅可以自适应地增强。包括我最近的工作在内的许多研究都揭示了视觉皮层在这种先天行为可塑性模型中的重要作用。我们的数据支持视觉皮层利用其下行的离皮质通路投射到脑干来增强其活动，这反过来又增强了脑干介导的OKR行为的表现。然而，这种皮质功能的确切机制仍有待明确阐明。我的研究计划旨在确定突触，细胞和电路机制，使皮层能够自适应地调节先天反射行为。介导OKR的脑干结构由不同类型的神经元组成。由于电路的神经布线形成了信息流和电路操作的神经基础，在这个建议中，我们将采用现代综合方法来揭示参与OKR可塑性的离皮质脑干电路的解剖结构。我们将确定脑干神经元群体接受长距离离皮质输入，并映射脑干群体之间的局部突触连接。这项研究将产生第一个基本的脑干回路的OKR行为的接线图。最终，它将提供对脑干群体在先天行为的皮质控制中的细胞类型特异性作用的见解。此外，技术和概念的进步将激发科学家对皮质功能的兴趣，特别是皮质对先天行为的影响。最后，该研究计划还将为加拿大的学术界和工业界培养高素质的年轻科学家。

A remarkable trait of the mammalian brain is the massive expansion of the neocortex, a phylogenetically modern structure. Despite the wealth of knowledge about its capability of sensory processing, we understand little of how the cortex contributes to behaviors, especially reflexes. Reflexive behaviors, like the escape from a threat, are innate involuntary motor actions that happen nearly instantaneously in response to external stimuli, and are critical for animals' survival. Although mediated by hardwired subcortical structures such as the brainstem, innate reflexes can also be modulated by the cortex, depending on prevailing condition and past experience. This cortical modulation of reflexes represents a fundamental evolutionary adaptation as it allows an organism to adjust its reflexive behaviors, which would be otherwise rigidly stereotyped, in response to dynamically changing environments. A prime example is the adaptive cortical control of the optokinetic reflex (OKR), an innate eye movement that stabilizes images on the retina as animals move through the environment. The OKR is highly plastic; in fact, its amplitude can be adaptively potentiated when other oculomotor reflexes are impaired. A number of studies including my recent work uncovered a prominent role of the visual cortex in this model of innate behavioral plasticity. Our data support that visual cortex uses its descending corticofugal pathway that projects to the brainstem to enhances it activity, which in turn boosts the performance of brainstem-mediated OKR behavior. However, the exact mechanisms underlying this cortical function remain to be clearly elucidated. My research program aims at identifying the synaptic, cellular, and circuit mechanisms that enable the cortex to adaptively modulate innate reflexive behaviors.******The brainstem structure mediating the OKR consists of diverse types of neurons. Since neural wiring of a circuit forms the neural basis of information flow and circuit operation, in this proposal we will employ a modern integrative approach to uncover the anatomy of corticofugal-brainstem circuits involved in OKR plasticity. We will identify brainstem neuronal populations receiving long-range corticofugal input, and map local synaptic connectivity between brainstem populations. This study will give rise to the first wiring diagram of the fundamental brainstem circuit of OKR behavior. And ultimately it will provide insights into the cell-type specific roles of brainstem populations in the cortical control of innate behaviors. In addition, the technical and conceptual advancements will inspire scientists interested in cortical functions, especially in cortical influence on innate behaviors. Finally, this research program will also prepare highly qualified young scientists for both academia and industry in Canada.**