IMAGING THE CIRCUIT MECHANISMS OF PERCEPTUAL LEARNING IN THE VISUAL CORTEX

描述（由申请人提供）：经验依赖性可塑性是感觉皮层的一个突出特征，并通过各种感觉经验在人的一生中发生。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感知的改善仍存在争议。拟议的职业发展计划的目的是获得基本的洞察神经网络水平的视觉感知学习的机制，同时建立一个独立的学术生涯在大学环境。候选人有相当丰富的经验，研究清醒行为小鼠的皮质功能，同时使用先进的光学技术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培训，以实现她的长期目标，即成为一名独立的科学家，研究健康和疾病状态下成人大脑皮层的网络水平可塑性。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。使用双光子钙成像来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，候选人最近发现，特定的视觉刺激会引起不同的神经元集合，这些集合对视觉刺激的反应比单个神经元更可靠。此外，相同的神经元集合自发激活，并响应于视觉刺激，这表明视觉属性的皮质表征是建立在内在的活动模式。候选人现在提出应用新的光学成像和操作技术来理解网络水平的活动如何被感官体验修改的机制。在指导阶段，她将使用快速成像和光遗传学技术来理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基底前脑胆碱能和GABA能输入在感知学习过程中对V1合奏活动的不同作用。在新的光学方法和啮齿动物行为的研究计划中概述的培训将装备候选人走上一个全面和富有成效的研究计划作为一个独立的研究人员。拟议的研究将成为未来研究成人可塑性在其他感官形式的基础，并将提供新的见解，了解如何学习信息编码整个大脑皮层。

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.