The Receptor Basis for the Neuromodulation of Olfactory Processing by Serotonin

血清素嗅觉处理神经调节的受体基础

• 批准号: 8751895
• 负责人: Andrew M Dacks
• 金额: $ 14.8万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8751895
• 关键词: Acute; Address; Afferent Neurons; Affinity; Behavioral Assay; Binding; Brain; Circadian Rhythms; Code; Complex; Data; Disease; Dissection; Drosophila genus; Genetic; Goals; Individual; Interneurons; Invertebrates; Knowledge; Lobe; Mediating; Mental Depression; Modeling; Molecular; Nervous system structure; Neuromodulator; Neurons; Odorant Receptors; Odors; Pattern; Physiological; Play; Process; Property; Receptor Activation; Research; Role; Schizophrenia; Second Messenger Systems; Sensory; Sensory Process; Serotonin; Signal Transduction; Smell Perception; Specificity; System; Testing; Time; Vertebrates; Work; base; expectation; flexibility; immunocytochemistry; information processing; innovation; nervous system disorder; neuroregulation; olfactory bulb; public health relevance; receptor; receptor expression; response; sensory system; serotonin 5 receptor; serotonin receptor; tool

DESCRIPTION (provided by applicant): Our brain must alter the way in which it processes sensory information based on the present physiological needs of the individual. For instance, our olfactory and gustatory systems are much more acute when we are hungry. To achieve this flexibility the nervous system relies on the release of "neuromodulators" which alter the response properties of neurons to optimize the ability of the nervous system to process information in the appropriate context. Neuromodulation is a ubiquitous feature of the nervous system and thus many neurological disorders, such as schizophrenia and depression, arise from dysfunctional neuromodulatory systems. Despite the importance of neuromodulation for healthy sensory processing, our ability to predict the consequences of neuromodulation has been limited due to the diversity of neuromodulatory receptor types expressed in the vertebrate nervous system (for instance, vertebrates possess 14 serotonin receptors). In this application, we propose to address this knowledge deficit by using a model sensory system with fewer receptors (5 serotonin receptors as opposed to 14), the olfactory system of Drosophila. The objective of this application is to determine the functional patterns of serotonin receptor expression within the olfactory system of Drosophila and the contribution of individual receptors towards the modulation of sensory input by serotonin. The long-term goal of this research is to determine how individual receptors expressed by distinct functional classes of neurons each contribute to the network level effects of neuromodulation. In the vertebrate and invertebrate olfactory system, serotonin enhances the odor-evoked responses within the physiological context of the waking state. However, without knowing the functional identity of neurons expressing each serotonin receptor, it is very difficult to determine which features of olfactory processing are directly altered resulting in the network-wide effects of serotonin. In Specific Aim 1 we will use immunocytochemistry in combination with genetic tagging to determine the transmitter content of the neurons expressing each of the four serotonin receptor types. To understand the contribution of any given receptor to the network-level effects of a neuromodulator, it is critical to understand the consequences of receptor activation for each functional neuronal type expressing a given receptor. In Specific Aim 2 we will manipulate the expression levels of a single serotonin receptor in a functionally discrete set of sensory neurons and use behavioral assays to determine the extent to which modulation of sensory neuron input by a single serotonin receptor influences olfactory processing.

描述（由申请人提供）：我们的大脑必须根据个人目前的生理需求改变其处理感官信息的方式。例如，当我们饥饿时，我们的嗅觉和味觉系统更加敏锐。为了实现这种灵活性，神经系统依赖于“神经调质”的释放，这些调质改变神经元的响应特性，以优化神经系统在适当环境中处理信息的能力。神经调节是神经系统的普遍特征，因此许多神经障碍，如精神分裂症和抑郁症，都是由功能失调的神经调节系统引起的。尽管神经调节对健康感觉处理的重要性，但由于脊椎动物神经系统中表达的神经调节受体类型的多样性（例如，脊椎动物拥有14种5-羟色胺受体），我们预测神经调节后果的能力受到限制。在这个应用程序中，我们建议使用一个模型的感觉系统，受体较少（5-羟色胺受体，而不是14），果蝇的嗅觉系统，以解决这个知识赤字。本申请的目的是确定5-羟色胺受体表达的功能模式内的果蝇的嗅觉系统和个人受体对5-羟色胺的感觉输入的调制的贡献。这项研究的长期目标是确定由不同功能类别的神经元表达的个体受体如何各自对神经调节的网络水平效应做出贡献。 在脊椎动物和无脊椎动物的嗅觉系统中，5-羟色胺在清醒状态的生理背景下增强气味诱发的反应。然而，在不知道表达每种5-羟色胺受体的神经元的功能特性的情况下，很难确定嗅觉处理的哪些特征直接改变，从而导致5-羟色胺的网络效应。具体目标 我们将使用免疫细胞化学结合遗传标记来确定表达四种5-羟色胺受体类型中每一种的神经元的递质含量。为了了解任何给定受体对神经调质的网络水平效应的贡献，关键是要了解表达给定受体的每种功能性神经元类型的受体激活的后果。在具体目标2中，我们将操纵一个单一的5-羟色胺受体在一组功能离散的感觉神经元的表达水平，并使用行为测定来确定在何种程度上调制的感觉神经元输入由一个单一的5-羟色胺受体影响嗅觉处理。