IMAGING THE CIRCUIT MECHANISMS OF PERCEPTUAL LEARNING IN THE VISUAL CORTEX

描述（由申请人提供）：经验依赖的可塑性是感觉皮质的一个显著特征，并在人的一生中通过各种感觉经验发生。研究知觉学习的神经机制将增强我们对成人大脑可塑性的理解，并为学习障碍的研究提供新的见解。虽然功能上的优势是显而易见的，但究竟是什么样的神经变化导致了感知能力的提高仍然存在争议。提出的职业发展计划旨在深入了解视觉感知学习的神经网络层面机制，同时在大学环境中建立独立的学术生涯。该候选人在研究清醒行为小鼠的皮质功能方面有丰富的经验，使用先进的光学技术同时监测数百个神经元的模式活动。她现在建议接受啮齿动物行为和尖端光学刺激工具的新训练，以实现她的长期目标，成为一名独立的科学家，研究健康和患病状态下成人皮层的网络级可塑性。她将在Rafael Yuste博士的指导下进行指导阶段，Rafael Yuste博士是开发光学方法并将其应用于皮层微电路结构和功能研究的世界专家。利用双光子钙成像技术同时测量清醒小鼠初级视觉皮层中数百个神经元的网络活动，该候选人最近发现，特定的视觉刺激会唤起不同的神经元集合，而这些神经元集合对视觉刺激的反应远比单个神经元可靠。此外，同样的神经元群在视觉刺激下会自发激活，这表明视觉属性的皮层表征是建立在内在活动模式之上的。该候选人现在建议应用新颖的光学成像和操作技术来理解感官经验如何改变网络级活动的机制。在指导阶段，她将使用快速成像和光遗传学技术来了解视觉刺激期间以及感知学习任务后自发活动期间感知学习的电路机制。在该奖项的独立阶段，候选人将使用这些新获得的技术技能来确定在感知学习过程中基底前脑胆碱能和gaba能输入对V1集合活动的不同作用。在研究计划中概述的新型光学方法和啮齿动物行为方面的培训将装备候选人作为独立研究人员开展全面而富有成效的研究计划。所提出的研究将成为未来研究其他感官模式的成人可塑性的基础，并将为学习到的信息如何在整个大脑皮层编码提供新的见解。

DESCRIPTION (provided by applicant): Experience-dependent plasticity is a prominent feature of the sensory cortices and occurs throughout one's lifetime by a variety of sensory experiences. Investigating the neural mechanisms of perceptual learning will enhance our understanding of plasticity in the adult brain and provide novel insights into learning disabilitie. Although the functional advantage is obvious, precisely what kinds of neural changes lead to improved perception is still under debate. The proposed career development plan aims to gain fundamental insights into the neural network-level mechanisms of visual perceptual learning, while establishing an independent academic career in a university setting. The candidate has considerable experience studying cortical function in awake behaving mice monitoring patterned activity in hundreds of neurons simultaneously using advanced optical techniques. She now proposes to undergo new training in rodent behavior and cutting-edge optical stimulation tools, to reach her long-term goal of becoming an independent scientist studying network-level plasticity in the adult cortex in healthy and diseased states. She will carry out the mentored phase under the guidance of Dr. Rafael Yuste, a world expert in developing optical methods and applying them to investigation of the structure and function of cortical microcircuit. Using two-photon calcium imaging to measure network activity from hundreds of neurons simultaneously in the primary visual cortex of awake mice, the candidate recently discovered that specific visual stimuli evoke distinct sets of neuronal ensembles and these ensembles respond far more reliably to visual stimuli than individual neurons. Furthermore, the same neuronal ensembles are activated spontaneously and in response to visual stimulation, suggesting that the cortical representation of visual attributes is built out of intrinsic activity patterns. The candidate now proposes to apply novel optical imaging and manipulation techniques to understand the mechanisms of how network-level activity is modified by sensory experience. During the mentored phase, she will use fast imaging and optogenetic techniques to understand the circuit mechanisms of perceptual learning during visual stimulation as well as during spontaneous activity following a perceptual learning task. In the independent phase of the award the candidate will use these newly acquired technical skills to determine the distinct roles of basal forebrain cholinergic and GABAergic inputs to V1 ensemble activity during perceptual learning. Training in novel optical methods and rodent behavior as outlined in the research plan will equip the candidate to embark on a comprehensive and fruitful research program as an independent researcher. The proposed studies will become a foundation for future studies on adult plasticity in other sensory modalities and will provide novel insights into how learned information is encoded throughout the cerebral cortex.