Neuromodulation in the olfactory system

描述(申请人提供)：值得注意的是，嗅球的颗粒细胞(GC)在整个生命过程中不断出生，为研究大脑中抑制性神经元的发育和成年神经发生提供了一个很好的神经元模型。就像在发育过程中出生的GC一样，成年嗅球中出生的细胞必须与现有的神经元成分建立功能连接，包括去甲肾上腺素系统的纤维。该系统在球状细胞的感觉信息处理中起着至关重要的作用。本申请中概述的目的是试图了解去甲肾上腺素系统调节嗅球GC功能的生理作用和细胞机制。在前两个目标中，我们建议研究去甲肾上腺素兴奋主嗅球和副嗅球GC的细胞机制和生理作用。在最后一个目标中，我们建议在嗅觉调节行为的背景下，确定去甲肾上腺素系统在成人GCs神经发生中的作用。 与公共卫生相关：新的神经元在成人大脑中诞生，也被称为成人神经发生，这一发现开启了一个充满希望的研究领域，因为它在治疗神经退行性疾病和衰老方面具有重建新电路的潜力。在显示成体神经发生的细胞中，有嗅球的抑制颗粒细胞。这些神经元在整个生命过程中不断诞生，为研究发育和成年神经发生提供了一个极好的神经元模型。在整个生命过程中，新生的颗粒细胞执行着生存和适当融入新环境的非凡任务。就像发育过程中出生的颗粒细胞一样，成年后出生的细胞必须与球茎现有的神经元组件建立功能连接。这些成分中有去甲肾上腺素系统的纤维，去甲肾上腺素系统是球茎中重要的神经调节系统。因此，与去甲肾上腺素系统相关的颗粒细胞功能的研究也具有医学意义。这个系统在整个大脑中有广泛的投射，在注意、焦虑和情绪等生理状态下的神经元兴奋性方面发挥着重要作用。

DESCRIPTION (provided by applicant): Remarkably, granule cells (GCs) of the olfactory bulb are continuously born throughout life, providing an excellent neuronal model for the study of both developmental and adult neurogenesis of inhibitory neurons in the brain. As with GCs born during development, cells born in the adult olfactory bulb must establish functional connections with existing neuronal components, including the fibers of the noradrenergic system. This system plays an essential role in sensory information processing in the bulb. The aims outlined in this application seek to understand the physiological role and cellular mechanisms by which the noradrenergic system modulates GC function in the olfactory bulb. In the first two aims, we propose to investigate the cellular mechanisms and physiological role of the excitatory action of noradrenaline on GCs in the main and accessory olfactory bulb. In the last aim, we propose to determine the role of the noradrenergic system on adult neurogenesis of GCs in the context of olfactory mediated behaviors. PUBLIC HEALTH RELEVANCE: The discovery that new neurons are born in the adult brain, also known as adult neurogenesis, has opened a promising area of research because of its therapeutic potential for rebuilding new circuits in neurodegenerative diseases as well as in aging. Among the cells that exhibit adult neurogenesis are the inhibitory granule cells of the olfactory bulb. These neurons are continuously born throughout life, providing an excellent neuronal model for the study of both developmental and adult neurogenesis. Throughout life, newly born granule cells perform the remarkable task of survival and proper integration into their new environment. As with granule cells born during development, the cells born in the adult must establish functional connections with existing neuronal components of the bulb. Among these components are the fibers of the noradrenergic system, an important neuromodulatory system in the bulb. Thus, the study of granule cell function in relation to the noradrenergic system also has medical implications. This system has extensive projections through the entire brain and plays an important role in neuronal excitability in physiological states such as attention, anxiety and emotions.