Behavioral readout of spatiotemporal codes dissected by holographic optogenetics

 描述(申请人提供)：感觉神经科学的两个最基本的问题是：1)刺激信息是如何由处于不同信息处理水平的神经元的活动来表示的？2)这一活动的哪些特征被高级大脑区域读出以指导行为？第一个问题已经成为不同感官模式的大量工作的主题。要回答第二个问题，需要建立神经元活动和行为之间的因果联系。在许多系统中，精细的时空活动模式是信息的神经表示的基础。在这些系统中，破译显著的神经编码将需要在监控行为的同时操纵具有良好时空分辨率的神经元集。最终，我们希望能够操纵组成神经回路的神经元的任意子集，并通过精确的时空控制来做到这一点。此外，我们希望在自然行为期间这样做，以提供从更广泛的活动杂音中辨别与行为相关的显著时空模式的能力。嗅觉是一种研究时空编码的理想系统。最近的研究表明，精细的时间尺度对于嗅觉信息处理是必不可少的，无论是在表征方面还是在行为读出方面。此外，时空联合活动扰动也会影响这个读数。在这里，我们建议在早期嗅觉的背景下开发和应用先进的全息光遗传技术，该技术将能够灵活地操纵网络中数十个神经元的时空放电模式，精确到单个神经元的分辨率和几毫秒的时间分辨率。检测和辨别气味刺激的进化关键能力背后的基本代码是以非常精细的时空分辨率携带的，我们使用这种新方法的目标是剖析这种代码的哪些特征是行为上可访问的。通过将最先进的细胞分辨率光遗传刺激工具与头部固定小鼠的嗅觉引导行为范例相结合，拟议的研究有望为剖析神经代码的哪些特征是行为可及的提供一种强大的新方法。

 DESCRIPTION (provided by applicant): Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by the activity of neurons at different levels of information processing? And 2) what features of this activity are read by the higher brain areas to guide behavior? The first question has been the subject of a large body of work across different sensory modalities. To answer the second question, one needs to establish a causal link between neuronal activity and behavior. In many systems, fine spatiotemporal patterns of activity underlie the neural representation of information. In these systems, deciphering the salient neural code will require manipulating sets of neurons with fine spatiotemporal resolution while monitoring behavior. Ultimately, we would like to be able to manipulate arbitrary subsets of the neurons comprising neural circuits, and to do so with precise spatiotemporal control. Further, we would like to do so during natural behavior, to provide the ability to discern the salient spatiotemporal patterns that are behaviorally relevant from the broader cacophony of activity. Olfaction is emerging as an ideal system for investigating spatiotemporal coding. Recent studies have revealed that fine temporal scales are essential to olfactory information processing, both in terms of representation and the behavioral readout. Moreover, joint spatiotemporal activity perturbations affect this readout. Here, we propose to develop and apply within the context of early olfaction an advanced holographic optogenetic technology, which will enable flexible manipulation of the spatiotemporal firing patterns of dozens of neurons within a network, down to single-neuron resolution and several milliseconds of temporal resolution. The essential code underlying the evolutionarily crucial ability to detect and to discriminate odor stimuli is carried at a very fine spatiotemporal resolution and our goal with this new approach is to dissect which features of this code are behaviorally accessible. By combining state-of-the-art tools for patterned cellular-resolution optogenetic stimulation with olfactory- guided behavioral paradigms in head-fixed mice, the proposed research is expected to contribute a powerful new approach for dissecting which features of neural codes are behaviorally accessible.