Dynamic Visual Activity in Temporal Cortex

描述（由申请人提供）：越来越多的证据表明，即使在成熟的大脑中，大脑内细胞构建块之间的功能连接也会积极重组。即便如此，这一观点尚未被普遍接受，部分原因是跟踪清醒的行为动物的这些变化在技术上具有挑战性。使单个神经元性质随经验变化的问题进一步复杂化的是，皮质包括许多细胞类型，并且来自申请人实验室的最近数据已经揭示，可塑性可以在这些群体中差异地表达。该提案的重点是视觉作为一个强大的模型系统，探索可塑性在正常大脑功能中的作用。待检验的一般假设是，有效的视觉处理依赖于下颞叶皮层（IT）内神经元的经验驱动的自适应放电模式，并且这种经验导致 兴奋性和抑制性神经元的不同生理变化。反过来，这些变化， 支持可衡量的行为优势。虽然神经反应的变化通常是缓慢的，但对神经活动的人工控制可以更快地诱导修改，并且这种修改 活动可以指导视觉上的行为。拟议的实验将支持旨在恢复或增强更高层次的视觉区域的适应性反应的努力。该提案有三个基本目标。第一个目的是清楚地表明长期熟悉对多个对象类的视觉处理的影响。实现这一目标的策略将是跟踪性能在一个快速识别任务与众所周知的和审判独特的刺激。第二个目的是确定视觉体验如何影响前IT皮层神经元的刺激编码。这将通过跟踪单个神经元和小群体活动来实现，方法是在第一个目标中开发的任务期间结合跨空间尺度的活动记录和使用仔细生成的视觉刺激。最终目的是直接操纵颞叶皮层的神经元活动来控制可塑性。该目标将利用申请人实验室中已经使用的光遗传学刺激方法来影响单次试验的神经反应，以诱导在第二个目标中观察到的各种可塑性。总之，这项工作的结果将有助于在细胞水平上的突触可塑性与灵长类动物的视觉行为的大量文献之间架起桥梁。这些研究的一个重要的具体焦点将是确定刺激，任务和生理条件下，兴奋和抑制 神经元通过长期的经验来适应它们的反应，并展示这种可塑性如何积极地影响行为。视觉经验可以深刻地改变IT中的视觉对象表征，这对于修复视觉系统和理解发育障碍的努力至关重要。使用一套创新的工具和方法，本提案中的项目将强调需要仔细跟踪行为动物的细胞活动，使用复杂而苛刻的真实的世界任务，其分辨率水平可能对未来的研究和模型至关重要，更高的大脑功能。

DESCRIPTION (provided by applicant): Mounting evidence shows that functional connections between the cellular building blocks within the brain actively reorganize, even in the mature brain. Even so, this view is not yet universally accepted in part because tracking these changes in the awake, behaving animal is technically challenging. Further complicating the question of changes in single neuron properties with experience is the fact that cortex comprises many cell types, and recent data from the applicant's laboratory has revealed that plasticity may be expressed differentially across these populations. This proposal focuses on vision as a powerful model system for exploring the role that plasticity plays in normal brain function. The general hypothesis to be tested is that effective visual processing relies on experience driven, adaptive firing patterns of neurons within the inferior temporal cortex (IT), and that this experience leads to differential physiological changes in excitatory and inhibitory neurons. These changes, in turn, support measurable behavioral advantages. Although changes in neural responses are typically slow, artificial control of neural activity can induce modification more rapidly, and this modified activity can guide visually directed behavior. The proposed experiments will support efforts aimed at reviving or augmenting adaptive responses in higher-level visual areas. The proposal has three fundamental aims. The first aim is to clearly demonstrate impact of long-term familiarity on visual processing for multiple object classes. The strategy for accomplishing this aim will be to track performance in a speeded recognition tasks with well-known and trial unique stimuli. The second aim is to determine how visual experience affects stimulus encoding by neurons in anterior IT cortex. This will be achieved by tracking single neuron and small population activity by combining recording of activity across spatial scales and using carefully generated visual stimuli during the tasks developed in the first aim. The final aim is to directly manipulate neuron activity in temporal cortex to control plasticity. This aim will leverage optogenetic stimulation methods already in use in the applicant's laboratory to affect neural responses on single trials in order to induce the kinds of plasticity observed in the second aim. Together, the results of this work will help bridge the large literature on synaptic plasticity at he cellular level with visual behavior in primates. An important specific focus of these studies will e to identify stimulus, task, and physiological conditions under which both excitatory and inhibitory neurons adapt their responses through long-term experience, and to show how this plasticity can positively influence behavior. That visual experience can profoundly alter visual object representations in IT is of critical importance to efforts directed at repair of the visual system nd in understanding development disorders. Using an innovative set of tools and approaches, the projects in this proposal will emphasize the need to carefully track cellular activity in behaving animals, using complex and demanding real world tasks, with a level of resolution that will likely prove essential for future studies, and models, of higher brain function.