Experience-driven plasticity of olfactory bulb odor representations

嗅球气味表征的经验驱动可塑性

• 批准号: 9285754
• 负责人: Takaki Komiyama
• 金额: $ 38.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9285754
• 关键词: Ablation; Address; Adult; Age; Aging; Alzheimer' s Disease; Animals; Area; Behavioral; Brain; Calcium; Chronic; Classification; Code; Data Set; Dementia; Discriminant Analysis; Discrimination; Discrimination Learning; Disease; Environment; Evolution; Exhibits; Future; Genetic; Head; Image; Impairment; Individual; Label; Learning; Learning Disorders; Methods; Monitor; Mus; Neurons; Neurosciences; Newborn Infant; Odors; Pattern; Perceptual learning; Population; Property; Publications; Research; Resolution; Role; Schizophrenia; Sensory; Sensory Process; Shapes; System; Techniques; Technology; Testing; Transgenic Organisms; adult neurogenesis; awake; base; cell type; cellular imaging; experience; experimental study; flexibility; frontier; granule cell; improved; in vivo calcium imaging; in vivo two-photon imaging; inhibitory neuron; innovation; insight; mitral cell; neurogenesis; neuromechanism; olfactory bulb; relating to nervous system; response; sensory stimulus; two-photon; young adult

 DESCRIPTION (provided by applicant): Through repetitive experience, one can better detect or discriminate sensory stimuli. This form of learning, termed perceptual learning, fundamentally shapes the way our brains process sensory information. The precise loci and mechanisms underlying perceptual learning are still debated. We address mechanisms of olfactory perceptual learning, focusing on the olfactory bulb, the first olfactory center of the brain. In th olfactory bulb, newborn inhibitory neurons are continuously integrated throughout adulthood, providing a remarkable potential for plasticity. Our central hypotheses are that 1) olfactory perceptual learning improves odor discriminability by the ensemble activity of mitral cells, the principal neurons in the olfactory bulb, and that 2) adult-born inhibitory neurons show particularly adaptive plasticity and support mitral cell plasticity during learning. To address thee ideas, we will apply in vivo two-photon calcium imaging chronically in the olfactory bulb of awake mice undergoing various olfactory experience paradigms over days. This is combined with mouse genetics to specifically label mitral cells and adult-born inhibitory neurons and ablate adult neurogenesis. We recently developed a system to chronically image the activity of defined populations of neurons in the olfactory bulb of awake mice (Kato et al. Neuron 2012, Kato et al. Neuron 2013). The current proposal extends this approach to characterize the dynamics of odor representations in the olfactory bulb during one-week-long experience paradigms. In Aim 1, we will characterize mitral cell responses to a pair of very similar odors during one-week-long experience in a passive exposure condition as well as several discrimination learning tasks. Our preliminary results suggest that discrimination learning enhances the discriminability of experienced odors by mitral cell ensemble activity. In Aim 2, we will test whether adult neurogenesis is necessary for olfactory perceptual learning and mitral cell plasticity. We will use genetic strategies to block adult neurogenesis and examine the effect on discrimination learning tasks. Furthermore, neurogenesis ablation will be combined with mitral cell imaging to test whether mitral cell plasticity during olfactory experience is altered with neurogenesis ablation. I Aim 3, we will evaluate the hypothesis that young adult-born inhibitory neurons show particularly pronounced and adaptive plasticity during olfactory experience. We will do this by directly imaging the activity of age-defined adult-born granule cells throughout the olfactory experience paradigms. These experiments combine cutting-edge technologies including chronic high-resolution two-photon imaging, behavioral tasks by head-fixed mice, and mouse genetics to label or ablate specific neuron types. They will reveal fine-scale circuit plasticity underlying perceptual learning and identify functional significance of adult neurogenesis. RELEVANCE: Dynamic and flexible processing of sensory information is essential for the well-being of animals in a changing environment and often impaired in neural disorders such as schizophrenia. We study neural mechanisms underlying olfactory perceptual learning, with a particular emphasis on adult neurogenesis within the olfactory bulb, the first olfactory center of the brain. The results will not only help us understand the functional significance of adult neurogenesis but also have implications in future treatments of learning disorders such as Alzheimer's disease and aging-related dementia.

 描述（由申请人提供）：通过重复的经验，可以更好地检测或区分感官刺激。这种形式的学习，被称为感知学习，从根本上塑造了我们大脑处理感官信息的方式。知觉学习的精确位点和机制仍然存在争议。我们解决嗅觉知觉学习的机制，重点放在嗅球，大脑的第一个嗅觉中心。在嗅球中，新生的抑制性神经元在整个成年期持续整合，提供了显着的可塑性潜力。我们的中心假设是：1）嗅觉知觉学习通过僧帽细胞（嗅球中的主要神经元）的整体活动来提高气味辨别能力，2）成年出生的抑制神经元在学习过程中表现出特别的适应性可塑性并支持僧帽细胞的可塑性。为了解决这些想法，我们将在清醒小鼠的嗅球中长期应用体内双光子钙成像，这些小鼠在几天内经历了各种嗅觉体验范例。这与小鼠遗传学相结合，可以特异性标记二尖瓣细胞和成人出生的抑制性神经元， 成人神经发生 我们最近开发了一种系统，用于长期成像清醒小鼠嗅球中定义的神经元群体的活动（Kato et al. Neuron 2012，Kato et al. Neuron 2013）。目前的建议扩展了这种方法来表征动态的气味表示在嗅球在一个星期长的经验范例。在目标1中，我们将描述二尖瓣细胞对一对非常相似的气味的反应，在一个为期一周的被动暴露条件下的经验，以及几个歧视学习任务。我们的初步研究结果表明，辨别学习提高了辨别经验的气味的二尖瓣细胞合奏活动。在目标2中，我们将测试成人神经发生是否是嗅觉知觉学习和二尖瓣细胞可塑性所必需的。我们将使用 遗传策略，以阻止成年神经发生和检查的歧视学习任务的影响。此外，神经发生消融将与二尖瓣细胞成像相结合，以测试神经发生消融是否改变了嗅觉体验期间的二尖瓣细胞可塑性。I目的3，我们将评估的假设，年轻的成年人出生的抑制神经元表现出特别明显的和适应性的可塑性在嗅觉的经验。我们将通过在整个嗅觉体验范例中直接成像年龄定义的成年出生的颗粒细胞的活动来做到这一点。这些实验结合了联合收割机尖端技术，包括慢性高分辨率双光子成像，头部固定小鼠的行为任务，以及标记或消融特定神经元类型的小鼠遗传学。他们将揭示知觉学习背后的精细回路可塑性，并确定成人神经发生的功能意义。 相关性：在不断变化的环境中，对感觉信息进行动态和灵活的处理对于动物的健康至关重要，并且经常在精神分裂症等神经疾病中受损。我们研究嗅觉知觉学习的神经机制，特别强调嗅球，大脑的第一个嗅觉中心内的成人神经发生。这些结果不仅有助于我们理解成人神经发生的功能意义，而且对未来治疗阿尔茨海默病和衰老相关性痴呆等学习障碍也有影响。