The role of immature olfactory sensory neurons in olfactory processing and plasticity

未成熟的嗅觉感觉神经元在嗅觉加工和可塑性中的作用

• 批准号: 8957722
• 负责人: Claire Elizabeth Jane Cheetham
• 金额: $ 14.98万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8957722
• 关键词: Adult; Air; Alzheimer' s Disease; Apoptosis; Area; Axon; Brain; Brain Injuries; Breathing; Calcium; Cells; Data; Dendrites; Disease; Electron Microscopy; Equilibrium; Exhibits; Goals; Image; Injury; Label; Life; Natural regeneration; Neurodegenerative Disorders; Neurons; Newborn Infant; Nose; Odors; Olfactory Epithelium; Olfactory Pathways; Output; Parkinson Disease; Plastics; Play; Population; Process; Recovery; Research; Role; Slice; Smell Perception; Stem cells; Stroke; Structure; Synapses; Testing; Therapeutic; Transgenic Organisms; Traumatic Brain Injury; Work; base; cell type; design; in vivo; mitral cell; nerve stem cell; neural circuit; neurogenesis; novel; olfactory bulb; olfactory sensory neurons; optogenetics; photoactivation; public health relevance; regenerative; repaired; restoration; sensory input; stem cell population; therapy design; two-photon

 DESCRIPTION (provided by applicant): The olfactory system is unusual in retaining a high level of plasticity throughout life, enabling olfactory circuits to regenerate following damage. Ou long-term goal is to determine how adult olfactory circuits balance this high level of plasticity with functional stability. One major contributor to the regenerative capacity of the olfactory system is lifelong neurogenesis of olfactory sensory neurons (OSNs) from stem cells in the nose. OSNs transmit sensory input to neurons in the olfactory bulb, where odor information is processed before being sent to olfactory cortical areas. However, the process by which new OSNs functionally incorporate into adult olfactory bulb circuits has been unclear. Understanding this process will be crucial in designing effective stem cell-based therapeutic strategies to repai damaged neural circuits in conditions such as neurodegenerative disease, stroke and traumatic brain injury. We will use a transgenic strategy to label and manipulate the activity of immature OSNs, in order to determine their role in olfactory bulb function and plasticity. First, using optogenetic photoactivation and electrophysiological recording in olfactory bulb slices, we will identify the olfactory bulb neurons with which immature OSNs form synaptic connections. Next, using in vivo 2-photon calcium imaging in combination with odor stimulation and optogenetic activation and silencing, we will determine the contribution made by immature OSNs to olfactory bulb output via mitral and tufted cells. Finally, using in vivo 2-photon imaging of synapses, we will determine the rate of recovery of immature and mature OSN synapse turnover following restoration of odor input. Successful completion of the proposed research will reveal the functional impact of incorporation of an endogeneous population of stem cell-derived neurons into adult neural circuits.