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

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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.**