Chronic imaging of odor-evoked activity in olfactory bulb circuits of awake mice

清醒小鼠嗅球回路中气味诱发活动的慢性成像

基本信息

批准号：
8364539
负责人：
JEFFRY S ISAACSON
金额：
$ 19.38万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2014-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The sense of smell plays an important role in our quality of life. However, the mechanisms governing the processing and representation of olfactory information in the brain are not well understood. In mammals, the olfactory bulb is a critical brain region responsible for the initial processing of olfactory information. Much of our current understanding of olfactory bulb function is based on previous studies using in vitro brain slices or acute preparations of anesthetized animals. While these approaches have provided valuable insight, much less is known about odor coding in awake, behaving animals. For example, what are the dynamics of odor representations in the same animal over long time scales (i.e. days, weeks, months) and how is odor coding in the olfactory bulb shaped by experience and learning in awake, behaving animals? To address these questions, we propose an experimental strategy using chronic 2-photon calcium imaging to study odor-evoked activity in the olfactory bulbs of awake mice. Specific Aim 1 proposes the development of an approach for the selective expression of the genetically-encoded calcium indicator GCaMP3 in principal (mitral/tufted) cells or local interneurons using a Cre-dependent, adeno-associated virus system. We hypothesize that this approach will provide single cell resolution of action potential-dependent calcium signals in large populations of neural ensembles that can be imaged chronically in awake, head fixed mice. Specific Aim 2 proposes imaging experiments to determine how odor-evoked responses of mitral cells and interneurons (granule cells) differ between the awake and anesthetized state. We will also use chronic imaging in awake animals to determine whether patterns of odor-evoked activity in neural ensembles are stable or dynamic over days of repeated testing. These experiments will provide new insight into the nature of odor coding in the awake brain. PUBLIC HEALTH RELEVANCE: Revealing how sensory information is processed and encoded by neural circuits is critical for understanding brain function. Here we propose a novel optical imaging approach to study how olfactory information is represented by large neuronal ensembles in awake mice.

描述（由申请人提供）：嗅觉在我们的生活质量中起着重要作用。然而，大脑中嗅觉信息处理和表达的机制尚不清楚。在哺乳动物中，嗅球是负责嗅觉信息初始处理的关键大脑区域。我们目前对嗅球功能的大部分了解都是基于之前使用体外脑切片或麻醉动物的急性制剂进行的研究。虽然这些方法提供了有价值的见解，但人们对清醒、行为动物的气味编码知之甚少。例如，同一动物在长时间尺度（即天、周、月）内的气味表征的动态是什么，以及清醒、行为动物的经验和学习如何塑造嗅球中的气味编码？为了解决这些问题，我们提出了一种实验策略，使用慢性 2 光子钙成像来研究清醒小鼠嗅球中气味诱发的活动。具体目标 1 提出开发一种方法，使用 Cre 依赖性腺相关病毒系统在主细胞（二尖瓣/簇状）或局部中间神经元中选择性表达基因编码的钙指示剂 GCaMP3。我们假设这种方法将在大量神经群中提供动作电位依赖性钙信号的单细胞分辨率，这些神经群可以在清醒、头部固定的小鼠中长期成像。具体目标 2 提出了成像实验，以确定二尖瓣细胞和中间神经元（颗粒细胞）的气味诱发反应在清醒状态和麻醉状态之间有何不同。我们还将使用清醒动物的慢性成像来确定神经系统中气味诱发的活动模式在几天的重复测试中是稳定的还是动态的。这些实验将为清醒大脑中气味编码的本质提供新的见解。公共健康相关性：揭示神经回路如何处理和编码感觉信息对于理解大脑功能至关重要。在这里，我们提出了一种新颖的光学成像方法来研究清醒小鼠的大型神经元群如何表示嗅觉信息。