Neuromodulation in the olfactory system

描述（由申请人提供）：值得注意的是，嗅球的颗粒细胞（GC）在整个生命过程中不断产生，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极好的神经元模型。与发育期间出生的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，包括去甲肾上腺素能系统的纤维。该系统在鳞茎的感觉信息处理中起着重要作用。本申请中概述的目的旨在了解去甲肾上腺素能系统调节嗅球中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对主嗅球和副嗅球GC兴奋作用的细胞机制和生理作用。在最后一个目标中，我们建议确定的作用，去甲肾上腺素能系统的成年神经发生的GC的嗅觉介导的行为。 公共卫生相关性：新的神经元在成人大脑中诞生的发现，也称为成人神经发生，开辟了一个有前途的研究领域，因为它具有在神经退行性疾病和衰老中重建新回路的治疗潜力。嗅球的抑制性颗粒细胞是表现成体神经发生的细胞之一。这些神经元在整个生命过程中不断产生，为发育和成人神经发生的研究提供了一个很好的神经元模型。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。与发育过程中产生的颗粒细胞一样，在成体中产生的细胞必须与灯泡中现有的神经元成分建立功能连接。在这些成分中，去甲肾上腺素能系统的纤维是球中重要的神经调节系统。因此，研究颗粒细胞功能与去甲肾上腺素能系统的关系也具有医学意义。该系统在整个大脑中有广泛的投射，在注意力、焦虑和情绪等生理状态下的神经元兴奋性中起着重要作用。

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.