The Functional Organization of Inhibition in the Olfactory Bulb In Vivo

体内嗅球抑制的功能组织

• 批准号: 8397200
• 负责人: Michael Nicholas Economo
• 金额: $ 4.92万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8397200
• 关键词: Action Potentials; Address; Animals; Area; Axon; Behavior; Brain; Cells; Code; Development; Disease; Distant; Environment; Fiber; Goals; Image; In Vitro; Individual; Injury; Interneurons; Lateral; Lead; Life; Location; Mediating; Microscopy; Molecular Genetics; Neurons; Odors; Olfactory Receptor Neurons; Output; Pathway interactions; Pattern; Population; Process; Reporter; Role; Sensory; Sensory Process; Shapes; Signal Transduction; Site; Structure; Synapses; System; Testing; To specify; Work; calcium indicator; extracellular; granule cell; in vivo; information processing; innovation; insight; neural circuit; novel; novel therapeutic intervention; olfactory bulb; olfactory stimulus; postsynaptic; research study; response; sensory system; tool; two-photon

DESCRIPTION (provided by applicant): In the olfactory bulb, a single synapse separates afferent sensory input and the principal neurons that project to higher cortical areas. Nevertheless, the vast majority of cells and connections in this structure are devoted to two distinct inhibitory circuits: one located superficially in the glomerular layer and one involving granule cells in infraglomerular layers. Soon after they were initially described, it was suggested that these inhibitory circuits might provide center-surround inhibition in an analogous fashion to other primary sensory areas. Nevertheless, the manner in which these circuits are activated by olfactory stimuli in vivo has yet to be demonstrated, and their importance in shaping olfactory bulb output remains controversial. In this proposal, the spread of inhibition laterally from the sites of olfactory receptor neuron input through the glomerular layer will be directly visualized t determine how lateral inhibition at this level might contribute to olfactory information processing In addition, the postsynaptic effect of inhibition arising from both lateral circuits will be assesed in identified olfactory bulb output neurons. These experiments will provide crucial insights into the role of lateral inhibitory circuits in vivo, and, by determining the differential effects of thse circuits on the excitability of different classes of output neurons, a better understanding of parallel pathways projecting to higher brain structures. PUBLIC HEALTH RELEVANCE: The representation of an animal's sensory environment in the brain comes about as a result of specific patterns of connectivity between neurons in sensory areas. To better understand how the olfactory system, and, more generally, all sensory systems, process sensory information, this proposal aims to describe the spatial spread of activity in inhibitory circuits and their impact on output neuron behavior in the olfactory bulb when the live animal is presented with odors. This course of study will provide new insights into the ways that information about odors are transformed by local circuits in the olfactory bulb so that we may better understand how the brain processes sensory signals generated in the animal's periphery and better address sensory deficits caused by injury and disease with new therapeutic approaches.

描述（由申请人提供）：在嗅球中，单个突触将传入感觉输入和投射到更高皮质区域的主要神经元分开。然而，该结构中的绝大多数细胞和连接致力于两种不同的抑制回路：一种位于肾小球层表面，另一种涉及肾小球下层的颗粒细胞。在最初描述它们后不久，有人建议 这些抑制回路可能以与其他主要感觉区域类似的方式提供中心-周围抑制。然而，这些回路在体内被嗅觉刺激激活的方式尚未得到证实，并且它们在塑造嗅球输出方面的重要性仍然存在争议。在该提案中，将直接可视化从嗅觉受体神经元输入位点通过肾小球层的横向抑制扩散，以确定该水平的横向抑制如何有助于嗅觉信息处理。此外，将在已识别的嗅球输出神经元中评估两个横向回路产生的抑制的突触后效应。这些实验将为体内侧抑制回路的作用提供重要的见解，并且通过确定这些回路对不同类别输出神经元兴奋性的差异影响，更好地理解投射到更高大脑结构的平行通路。 公共卫生相关性：动物大脑中感觉环境的表征是感觉区域神经元之间特定连接模式的结果。为了更好地理解嗅觉系统，更广泛地说，所有感觉系统如何处理感觉信息，本提案旨在描述当活体动物出现气味时，抑制回路活动的空间传播及其对嗅球输出神经元行为的影响。本研究课程将为嗅球局部回路转换气味信息的方式提供新的见解，以便我们更好地了解大脑如何处理动物外围产生的感觉信号，并通过新的治疗方法更好地解决由损伤和疾病引起的感觉缺陷。