The Receptor Basis for Serotonergic Modulation of Olfaction Across Multiple BrainAreas

跨多个脑区嗅觉的血清素调节的受体基础

• 批准号: 10403591
• 负责人: Andrew M Dacks
• 金额: $ 38.28万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10403591
• 关键词: Address; Affect; Atlases; Behavior; Behavioral Assay; Biological Models; Biophysics; Brain; Brain region; Cells; Code; Complex; Drosophila genus; Electrophysiology (science); Goals; Horns; Image; Individual; Interneurons; Invertebrates; Knowledge; Lateral; Lobe; Modeling; Nervous system structure; Neuromodulator; Neurons; Neuropil; Odors; Olfactory Pathways; Output; Physiological; Population; Positioning Attribute; Process; Property; Regulation; Research; Resolution; Role; Sensory; Serotonin; Smell Perception; Synapses; System; Testing; Transgenic Organisms; base; biophysical properties; cholinergic; connectome; dynamic system; experimental study; flexibility; innovation; knock-down; nanometer resolution; nervous system disorder; neuronal excitability; neuroregulation; olfactory bulb; patch clamp; presynaptic; receptor; receptor expression; reconstruction; response; sensory system; serotonin receptor; tool

Project Summary. Sensory networks continuously fine-tune how they process information to meet ongoing physiological demands. The nervous system achieves this flexibility via the release of “neuromodulators” which alter the biophysical and synaptic properties of individual neuron classes within a network. This adjusts the influence of each class to optimize network dynamics for the appropriate context. Neuromodulation is ubiquitous and many neurological disorders result from, or are associated with, dysfunctional neuromodulatory systems. Despite the importance of neuromodulation for healthy sensory processing, our ability to predict the consequences of neuromodulation is limited by the diversity of modulatory receptors expressed by different classes of neurons. Each receptor has different effects and each class of neuron supports different features of sensory coding, so the effects of neuromodulation can be complex. We propose to address this issue in a genetically tractable model with fewer neurons and modulatory receptors; the olfactory system of Drosophila. The objective of this application is to determine how serotonin (5-HT) receptor subtypes affect key neuronal classes and the consequences for olfactory processing and odor-guided behavior. The long-term goal of this research is to determine the mechanistic basis for neuromodulation of sensory network dynamics. In vertebrate and invertebrate olfactory systems, the effects of 5-HT on odor-evoked responses vary across different neuron classes. However, it is difficult to determine how 5-HT alters olfactory processing without knowing the consequences of activating the 5-HT receptors expressed by each class. We recently completed a comprehensive atlas of 5-HT receptor expression within the olfactory system, so we now propose to manipulate the expression of individual 5-HT receptors in specific classes of neurons to determine how 5-HT affects individual neuron classes, the consequences for odor coding across olfactory brain regions and odor- guided behavior. In addition, we will use one of the first whole brain, nanometer resolution EM connectomes to establish single cell resolution connectivity rules of 5-HT neurons with each olfactory neuron class examined in this proposal. In Specific Aim 1 we will determine the receptor basis for the effects of 5-HT on local inhibitory networks within the first olfactory neuropil (the antennal lobe or “AL”). In Aim 2 we will determine the contribution of direct modulation of cholinergic AL output neurons to the overall effects of 5-HT on olfactory information sent to downstream processing stages. Finally, in Aim 3 we will determine how 5-HT receptors modulate GABAergic AL output neurons that promote olfactory attraction. These experiments will establish how the overall effects of 5-HT emerge from neuron class-specific expression of 5-HT receptors, thus addressing a critical gap in our knowledge of healthy sensory processing.

项目摘要。感觉网络不断微调他们如何处理信息，以满足持续的 生理需求。神经系统通过释放“神经调质”来实现这种灵活性， 改变网络内单个神经元类的生物物理和突触特性。这将调整 每个类的影响，以优化网络动态适当的上下文。神经调节是 普遍存在的和许多神经系统疾病是由功能失调的神经调节功能引起的，或与之相关。 系统.尽管神经调节对于健康的感觉处理很重要，但我们预测神经调节的能力仍然是有限的。 神经调节的结果受限于由不同神经元表达的调节受体的多样性。 类神经元。每种受体都有不同的作用，每类神经元支持不同的功能。 感觉编码，因此神经调节的效果可能是复杂的。我们建议以 遗传上易于控制的模型，神经元和调节受体较少;果蝇的嗅觉系统。 本申请的目的是确定5-羟色胺（5-HT）受体亚型如何影响关键的神经元 类别和嗅觉处理和气味引导行为的后果。长期目标是 研究的目的是确定感觉网络动力学的神经调节的机制基础。 在脊椎动物和无脊椎动物的嗅觉系统中，5-HT对气味诱发反应的影响各不相同 在不同的神经元类别中。然而，很难确定5-HT如何改变嗅觉加工 而不知道激活由每类表达的5-HT受体的后果。我们最近 完成了嗅觉系统内5-HT受体表达的综合图谱，因此我们现在提出 操纵特定类别神经元中单个5-HT受体的表达，以确定5-HT如何 影响单个神经元类别，嗅觉大脑区域和气味编码的后果- 引导行为。此外，我们将使用第一个全脑，纳米分辨率EM连接体之一， 建立5-HT神经元的单细胞分辨连接规则，检查每个嗅觉神经元类别， 这个提议。在具体目标1中，我们将确定5-HT对局部抑制作用的受体基础。 第一嗅觉神经元（触角叶或“AL”）内的网络。在目标2中，我们将确定 胆碱能AL输出神经元的直接调制在5-HT对嗅觉的整体效应中的作用 发送到下游处理阶段的信息。最后，在目标3中，我们将确定5-HT受体如何 调节促进嗅觉吸引的GABA能AL输出神经元。这些实验将建立 5-HT的总体效应如何从5-HT受体的神经元类特异性表达中出现，从而 解决了我们对健康感官处理知识的一个关键空白。

项目成果

Local synaptic inputs support opposing, network-specific odor representations in a widely projecting modulatory neuron.

局部突触输入在广泛投射的调节神经元中支持相反的、网络特定的气味表征。

• DOI: 10.7554/elife.46839
• 发表时间: 2019
• 期刊: eLife
• 影响因子: 7.7
• 作者: Zhang,Xiaonan;Coates,Kaylynn;Dacks,Andrew;Günay,Cengiz;Lauritzen,JScott;Li,Feng;Calle-Schuler,StevenA;Bock,Davi;Gaudry,Quentin
• 通讯作者: Gaudry,Quentin

Circadian Clocks: Mosquitoes Master the Dark Side of the Room.

昼夜节律时钟：蚊子主宰房间的黑暗面。

• DOI: 10.1016/j.cub.2020.06.069
• 发表时间: 2020
• 期刊: Current biology : CB
• 作者: Sizemore,TylerR;Dacks,AndrewM
• 通讯作者: Dacks,AndrewM