Development and refinement of functional properties of adult-born olfactory bulb neurons

项目摘要 感觉系统必须是可塑性的，才能在整个生命周期内进行学习；然而，大脑区域 参与处理感官信息的人在正常衰老过程中可塑性显著下降 并与神经精神疾病和神经退行性疾病协同工作。例如，嗅觉缺陷是 估计影响到美国一半以上的老年人口。它有一个很有希望的特性 然而，嗅觉系统具有终身可塑性的广泛能力。啮齿动物的嗅球(OB)是 由于正在进行的神经发生，成人大脑中最具可塑性的区域之一。成人出生颗粒细胞(AbGC) 是数量最多的成年出生的神经元，在它们成熟的过程中，它们会形成突触 并集成到OB电路中。然而，关于这一问题的信息仍然有限 AbGC对刺激的反应在体内的发展。该项目旨在使用体内纵向多光子 单个abGC气味诱发反应的钙成像以表征(1)abGC何时首次成为 对嗅觉刺激的反应以及单个神经元的反应如何随着时间的推移而变化 成熟和(2)如何在嗅觉学习的背景下修改这一过程。初步数据 表明在种群水平上，abGC在发育早期对气味更敏感。这 支持这样一种假设，即abGC最初广泛的代表可以被改进以增强它们的选择性 当它们成熟时会有特殊的气味。随着时间的推移，分析识别出的细胞的气味响应曲线将允许 单个细胞气味响应量、稳定性和气味选择性的时间过程的研究 在单个细胞水平上。此外，训练小鼠在关键时期的可操作性行为任务 AbGC队列将提供对气味暴露和气味奖赏关联对 ABGC反应的稳定性和流行率。总之，这些实验将为我们提供重要的见解 成体神经元整合到现有回路中的过程和可能的机制 这个过程可以通过学习来修改，以增强感觉处理。

Project Summary Sensory systems must be plastic in order to allow learning throughout the lifespan; however, brain regions involved in processing sensory information undergo a significant decline in plasticity during both normal aging and in concert with neuropsychiatric and neurodegenerative diseases. For example, olfactory deficits are estimated to affect more than half of the elderly population in the United States. One promising feature of the olfactory system, however, is its extensive capability for lifelong plasticity. In rodents, the olfactory bulb (OB) is one of the most plastic areas of the adult brain due to ongoing neurogenesis. Adult-born granule cells (abGCs) are the most numerous population of adult-born neurons, and during their maturation, they develop synapses with existing cells and integrate into the OB circuit. However, there is still limited information about the development of abGCs’ responses to stimuli in vivo. This project aims to use longitudinal in vivo multiphoton calcium imaging of individual abGCs’ odor-evoked responses to characterize (1) when abGCs first become responsive to olfactory stimuli and how the responses of individual neurons change over time as the cells mature and (2) how this process may be modified in the context of olfactory learning. Preliminary data indicates that on a population level, abGCs are more responsive to odors early during their development. This supports the hypothesis that abGCs’ initially broad representations may be refined to enhance their selectivity for particular odors as they mature. Analyzing the odor response profiles of identified cells over time will allow the investigation of the timecourse of an individual cell’s odor response magnitude, stability and odor selectivity on a single cell level. In addition, training mice in an operant behavioral task during the critical period of a cohort of abGCs will provide insight into the effects of odor exposure and odor-reward associations on the stability and prevalence of abGC responses. Together, these experiments will provide important insights into the process by which adult-born neurons integrate into an existing circuit and possible mechanisms by which this process may be modified by learning in order to enhance sensory processing.