Editing the Neural Basis of Perception

项目总结： 神经计算需要数以千计相互关联且通常遗传上相似的生物的协同努力 神经元。这些神经元形成物理上相互交织的网络和子网络，它们共同作用以放大 并加强感官感知或选择运动动作。这种共同活跃的乐团是已知的 优先相互连接，并且可以代表神经处理的功能元素，具有独特的 属性，如模式完成和乐团之间的竞争。在这项提议中，我将获得 从机制上理解协同活动神经元如何相互作用 清醒小鼠的个体和神经细胞群。我将研究：锥体细胞群是如何 在视觉任务中，与其他锥体细胞和局部抑制神经元相互作用，这些集合如何影响 运动行为，以及特定的合奏如何对来自其他皮质区域的信息做出反应。尽管 在大脑皮层编码中集合的潜在重要性，这些组的混合性质使得它们 特别难研究。虽然传统的光遗传技术可以操纵基因识别 一个区域中的神经元，它们不能选择性地操纵混合在一起的神经元，这些神经元只有在它们的 功能属性。重要的是，新的多光子光遗传技术开始允许操控 然而，这种技术还需要进一步的发展。在K99阶段 在这项提议中，我将通过开发新的多光子光学系统来继续我的培训 并通过刺激和使用这些技术了解皮质功能。通过将这些新的光纤 我已经开发了用于体内多光子使用的新型光学蛋白技术，我现在有了 能够以前所未有的精确度写入或编辑多个神经元的神经活动。通过 改变视觉感知过程中的整体活动我将确定个体的因果贡献 神经元以及神经元群体对感觉编码。在R00阶段，通过 运动皮质I将揭开这些群体的行为影响，探索运动合奏在 运动动作，并研究神经元如何跨通道相互作用。能够编辑和监控活动 对于获得对感知和行动的机械性理解来说，神经子网络是至关重要的。这个 我们从这个提案中得出的结论将有助于描述所有信息是如何在大脑皮层中呈现的，但是 只有用先进的技术才能达到。

Project Summary: Neural computation requires the coordinated effort of thousands of interrelated and often genetically similar neurons. These neurons form physically intermingled networks and subnetworks that act together to amplify and strengthen sensory perceptions or select motor action. Such co-active ensembles are known to be preferentially interconnected, and may represent a functional element of neural processing with unique properties, such as pattern completion and competition between ensembles. In this proposal I will gain a mechanistic understanding of how ensembles of co-active neurons interact by probing the function of individual and groups of neurons in an awake mouse. I will examine: how ensembles of pyramidal cells interact with other pyramidal cells and local inhibitory neurons in a visual task, how these ensembles influence motor behavior, and how specific ensembles respond to information from other cortical areas. Despite the potential importance of ensembles in cortical coding, the intermixed nature of these groups has made them particularly hard to study. While conventional optogenetic techniques can manipulate genetically identified neurons in a region, they are incapable of selectively manipulating intermingled neurons that differ only by their functional properties. Critically, new multiphoton optogenetic techniques are beginning to allow manipulation of cells chosen by their activity alone, however such techniques require further development. In the K99 phase of this proposal, I will continue my training through the development of novel optical systems for multiphoton stimulation and through use of these technique understand cortical function. By combining these new optical techniques with novel opsins designed for in vivo multiphoton use that I have already developed, I now have the ability to write in or edit neural activity across many neurons with a precision never before possible. By altering ensemble activity during visual perception I will determine the causal contributions of individual neurons as well as populations of neurons to sensory coding. In the R00 phase, through manipulations in motor cortex I will unravel the behavioral impact of these groups, probing the role motor ensembles play in motor action, and study how neurons interact across modalities. The ability to both edit and monitor the activity of neural subnetworks is critical to gaining a mechanistic understanding of perception and action. The conclusions we draw from this proposal will help to describe how all information is presented in the cortex, but can only be reached with advanced techniques.