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）刺激信息如何由不同信息处理水平的神经元活动表示？2）这种活动的哪些特征被高级大脑区域读取，以指导行为？第一个问题一直是跨不同感官模式的大量工作的主题。要回答第二个问题，我们需要在神经元活动和行为之间建立因果关系。在许多系统中，精细的时空活动模式是信息的神经表征的基础。在这些系统中，破译突出的神经代码将需要在监控行为的同时以精细的时空分辨率操纵神经元集。最终，我们希望能够操纵构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实现。此外，我们希望在自然行为中这样做，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，精细的时间尺度是必不可少的嗅觉信息处理，无论是在表征和行为读出。此外，联合时空活动扰动影响这一读数。在这里，我们建议在早期嗅觉的背景下开发和应用一种先进的全息光遗传学技术，该技术将能够灵活地操纵网络内数十个神经元的时空放电模式，低至单神经元分辨率和几毫秒的时间分辨率。基本代码的进化至关重要的能力，检测和区分气味刺激进行在一个非常好的时空分辨率和我们的目标与这种新的方法是剖析这种代码的功能是行为上可访问的。 通过在头部固定的小鼠中将用于模式化细胞分辨率光遗传学刺激的最先进工具与嗅觉引导的行为范例相结合，预计所提出的研究将为剖析神经代码的哪些特征在行为上是可访问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.