Active sensing at the sensory surface: glomerular signals for olfactory navigation by freely-moving mice

我们的感官不是被动的。相反，我们通过抽样运动积极寻求相关信息。 然而，感觉系统的实验通常限制采样运动以简化刺激传递 并允许大规模成像和电生理学。但是感觉系统是否在 限制还是自由取样仍然是一个悬而未决的问题。老鼠的嗅觉系统呈现出完美的 有机会解决这些问题。老鼠在不断的运动，积极嗅在他们的整个 环境在这里，我们将建立一系列创新技术来将感官输入成像到 嗅觉系统，并控制输入光遗传学，所有这些都在不受限制的小鼠中进行。我们将执行这些 在我们已经建立的不受限制的嗅觉导航测定的背景下的实验。老鼠学习 这一任务迅速，并解决了任务的气味浓度梯度。使用实时视频 通过跟踪鼻子的运动和呼吸的热记录，我们可以监测它们的采样策略。 我们发现，小鼠发展出一致的动作，这些动作精确同步， sniff循环重要的是，这些行为动力学只有在动物能够移动时才会显示出来。 自然在环境中。在目标1中，我们将对嗅球小球的感觉输入进行成像 在这次航行任务中。在二尖瓣和簇状细胞中， 指示剂，其具有比更广泛使用的钙指示剂快得多的动力学。大家可以 捕捉对嗅球的输入的快速时间模式。为了给自由移动的老鼠成像， 实现一种微型显微镜设计，可以成像整个背表面的嗅球， 自由移动的老鼠在aim2中，我们将开发一种用虚构羽流驱动导航行为的方法 我们可以通过光遗传学控制。使用在嗅觉中表达Rhodopsin-2的小鼠系 感觉神经元，我们将提供光刺激与小鼠的运动和吸入闭环。在 在这个资助的时间轴上，我们将使用这种技术来创建输入幅度的虚构梯度， 被认为代表肾小球水平气味浓度的编码线索。我们建立了 行为任务，使我们能够在嗅觉导航过程中研究主动采样。在本提案中，我们将 使用这个框架进行初步研究，以了解潜在的神经机制。这项工作 将促进我们对如何通过采样行为优化感官输入的理解， 在精神分裂症和孤独症等神经系统疾病中会出现问题。

Our senses aren’t passive. Rather, we actively seek relevant information via sampling movements. However, experiments in sensory systems often restrict sampling movements to simplify stimulus delivery and allow large scale imaging and electrophysiology. But whether sensory systems function equivalently in restraint vs free sampling remains an open question. The mouse olfactory system presents a perfect opportunity to address these issues. Mice are in constant motion, actively sniffing throughout their environment. Here, we will establish an array of innovative techniques to image the sensory input to the olfactory system, and to control that input optogenetically, all in unrestrained mice. We will perform these experiments in the context of an unrestrained olfactory navigation assay we have established. Mice learn this task rapidly, and solve the task by following the odor concentration gradient. Using real-time video tracking of nose movements and thermal recording of respiration, we can monitor their sampling strategies. We have found that mice develop a consistent repertoire of movements that are precisely synchronized to the sniff cycle. Importantly, these behavioral dynamics are only revealed when an animal is able to move naturally in the environment. In aim 1, we will image sensory input to the glomeruli of the olfactory bulb during this navigation task. In mitral and tufted cells, we will express genetically encoded glutamate indicators, which have much faster kinetics than the more widely-used calcium indicators. We can thus capture fast temporal patterning of the input to the olfactory bulb. To image in freely-moving mice, we will implement a miniature microscope design that can image the entire dorsal surface of the olfactory bulb in freely-moving mice. In aim 2, we will develop a method for driving navigation behavior with fictive plumes that we control optogenetically. Using a mouse line that expresses ChannelRhodopsin-2 in olfactory sensory neurons, we will deliver light stimuli in closed loop with the mouse’s movements and inhalations. In the timeline of this grant, we will use this technique to create fictive gradients of input amplitude, a neural coding cue that is thought to represent odor concentration at the glomerular level. We have established a behavioral task that allows us to study active sampling during olfactory navigation. In this proposal we will perform the initial studies using this framework to understand the underlying neural mechanisms. This work will advance our understanding of how we optimize our sensory input through sampling behavior, a process that goes awry in neurological disorders such as schizophrenia and autism.