Role of neuronal ensembles in visual processing

项目摘要 视觉是人类最依赖的感觉形式，通过 并建立有意义的社会关系。因此，视觉系统的紊乱 往往会导致严重的人际关系和经济困难。尽管已经取得了很大的进展 解剖了视网膜对光产生动作电位的机制， 令人惊讶的是，关于大脑实际上是如何解释和理解这些信息的，人们知之甚少 信号。我建议利用尖端光学技术来阐明神经元如何 集合(共同活动的细胞群)编码初级视觉皮质(V1)的感觉信息， 新皮质区域，需要执行认知要求高的任务，包括视觉 歧视。V1中的系综显示出具有可重复的空间和时间的活动模式 定义大脑皮层微电路功能词汇的结构和可能的载体 与动物的视野和内部状态有关的信息。然而，如何 这些计算出现了，无论它们是否由独立的电路组成，以及范围 它们为视觉感知提供了模板，但仍不清楚。要解决这些问题 问题是，我将进行慢性双光子全息钙成像的一个一致 清醒小鼠学习视觉引导任务的V1神经元数量。以同样的方式成像 区域纵向将使我们能够确定皮质集合是如何出现或被重塑为 视觉特征变得任务突出(目标1)。然后，为了测试它们的功能作用，我会人工 用双光子全息光遗传学激活已识别的神经系综以测试 他们的活动足以产生一种感知，并引发预期的视觉唤起 回应(目标2)。这些实验的成功完成将测试神经 合奏确实是大脑皮层功能的基石，并将提供一种新的理解 感知和行为之间的联系。此外，目前的项目将展示 大脑皮层集合如何在学习过程中将视觉信息与非感觉变量相结合 并将在更全面地理解视觉方面取得新的进展，这是 解决失明等疾病缺乏有效治疗选择的问题。

Project Summary Vision is the sensory modality that humans depend on most to navigate through the world and to establish meaningful social relationships. Disorders of the visual system therefore often lead to severe interpersonal and economic hardships. Although much progress has been made dissecting the retinal mechanisms that generate action potentials in response to light, surprisingly little is known about how the brain actually interprets and contextualizes these signals. I propose to leverage cutting-edge optical technologies to clarify how neuronal ensembles (coactive groups of cells) encode sensory information in primary visual cortex (V1), the neocortical region which is required to perform cognitively demanding tasks including visual discrimination. Ensembles in V1 exhibit activity patterns with reproducible spatial and temporal structures which define the functional vocabulary of cortical microcircuits and that likely carry information pertaining to both the visual field and to the internal state of the animal. Yet how these computations emerge, whether they are comprised of independent circuits, and the extent to which they provide a template for visual perception remain unknown. To address these questions, I will perform chronic two-photon holographic calcium imaging of a consistent population of V1 neurons in awake mice learning a visually-guided task. Imaging the same region longitudinally will allow us to identify how cortical ensembles emerge or are remodeled as visual features become task-salient (Aim 1). Then, to test their functional role, I will artificially activate identified neural ensembles with two-photon holographic optogenetics to test whether their activity is sufficient to generate a percept and to elicit the expected visually-evoked response (Aim 2). Successful completion of these experiments will test whether neural ensembles are indeed building blocks of cortical function and will provide a new understanding of the link between perception and behavior. Furthermore, the current project will demonstrate how cortical ensembles integrate visual information with non-sensory variables during learning and will yield new inroads towards a more complete understanding of vision, a prerequisite to addressing the paucity of effective treatments options for illnesses such as blindness.