Imaging rapid, use-dependent plasticity of structural and functional circuits in the adult somatosensory cortex

作为人类，我们理所当然地认为我们有能力形成对外部世界的准确感官知觉，或者学习可能在日常基础上需要的感觉运动任务的新方面。例如，一名新的医科学生将使用他们的触觉来学习如何评估病人的脉搏、呼吸质量或进行一项需要灵巧操作的新手术。为了让我们进行这些活动，我们大脑中的神经元回路必须通过调整现有连接之间的交流强度或形成新的连接来改变。尽管在理解我们的大脑如何变化方面已经取得了相当大的进展，但迄今为止进行的大部分工作都是在死后组织中完成的，或者使用的成像技术无法实时跟踪我们大脑的异常快速反应。因此，对于触觉刺激或学习如何在完整的活体大脑皮层中引起快速的结构和功能变化，我们知之甚少。我研究的主要目的是使用新的成像技术，使我能够在活体动物中可视化，大脑皮层如何积极地处理触觉信息或在感觉刺激或学习新的触觉联系时形成新的回路。此外，我将剖析触发大脑皮层电路快速变化的神经化学和分子机制。进行这些实验将提供有关介导快速形式的感觉学习、习惯化和敏化的神经生物学机制的关键信息。此外，知道如何用一种相对无害的触觉刺激形式来调节或启动皮层回路，可能有助于治疗与异常皮层反应性相关的神经病理状况(例如：幻肢感觉，纤维肌痛，精神分裂症)或损伤引起的皮层回路中断后的功能恢复。

As humans, we take for granted our abilities to form an accurate sensory perception of the outside world or learn new facets of a sensory-motor task that may be required on a day-to-day basis. For example, a new medical student will use their sense of touch to learn how to assess a patients' pulse, quality of breathing or perform a new surgery that requires dexterous maneuvering. In order for us to carry out these activities, the neuronal circuits within our brain must change by adjusting the strength of communication between existing connections or by forming new ones altogether. Although considerable progress has been made towards understanding how our brain changes, much of the work conducted thus far has been done in post-mortem tissue or using imaging techniques that cannot track the exceptionally fast responses of our brain in real-time. Consequently, very little is known about how tactile stimulation or learning can induce rapid structural and functional changes in the cerebral cortex of the intact, living brain. The primary aims of my research will be to use new imaging technologies that will allow me to visualize in the living animal, how the cerebral cortex actively processes tactile information or forms new circuits during sensory stimulation or whilst learning new tactile associations. Further, I will dissect the neurochemical and molecular mechanisms that trigger rapid changes in cerebral cortical circuitry. Performing these experiments will provide critical information regarding the neurobiological mechanisms that mediate rapid forms of sensory learning, habituation and sensitization. Furthermore, knowing how to tune or prime cortical circuits with a relatively innocuous form of tactile stimulation may facilitate the treatment of neuropathological conditions associated with aberrant cortical responsiveness (eg. phantom limb sensations, fibromyalgia, schizophrenia) or the recovery of functions after injury-induced disruptions to cortical circuits.