IMAGING THE CIRCUIT MECHANISMS OF PERCEPTUAL LEARNING IN THE VISUAL CORTEX

描述(申请人提供)：依赖经验的可塑性是感觉皮质的一个显著特征，通过各种感觉经验发生在人的一生中。研究知觉学习的神经机制将加深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。尽管功能优势是显而易见的，但究竟是哪种神经变化导致感知能力的改善仍在争论中。拟议的职业发展计划旨在获得对视觉知觉学习的神经网络层面机制的基本见解，同时在大学环境中建立独立的学术生涯。这位候选人在研究清醒行为小鼠的皮质功能方面拥有相当丰富的经验，同时使用先进的光学技术监测数百个神经元的模式活动。她现在建议在啮齿动物行为和尖端光学刺激工具方面接受新的培训，以实现她的长期目标，即成为一名独立科学家，研究健康和疾病状态下成年大脑皮质的网络水平可塑性。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研究皮质微电路结构和功能的世界专家。使用双光子钙成像技术同时测量清醒小鼠初级视皮层中数百个神经元的网络活动，这位候选人最近发现，特定的视觉刺激可以唤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要可靠得多。此外，同样的神经元集合被自发地激活，并对视觉刺激做出反应，这表明视觉属性的皮质表征是由内在活动模式构建的。这位候选人现在提议应用新的光学成像和操纵技术来理解网络水平的活动如何被感觉体验改变的机制。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知觉学习任务后的自发活动中知觉学习的电路机制。在奖项的独立阶段，候选人将使用这些新获得的技术技能来确定在知觉学习期间，基底前脑胆碱能和GABA能输入到V1整体活动中的不同角色。研究计划中概述的新颖光学方法和啮齿动物行为方面的培训将使候选人具备作为独立研究员开始全面和富有成效的研究计划的能力。这项拟议的研究将成为未来研究成人在其他感觉方式下的可塑性的基础，并将为学习到的信息如何在大脑皮层中编码提供新的见解。

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.