Mechanisms of flexible neural decoding in the fly olfactory system

果蝇嗅觉系统灵活的神经解码机制

• 批准号: 10231888
• 负责人: Kristyn Lizbinski
• 金额: $ 6.64万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231888
• 关键词: Address; Afferent Neurons; Algorithms; Area; Automobile Driving; Behavior; Behavioral; Binding; Biology; Brain; Cells; Code; Complex; Data; Dopamine; Dopamine Receptor; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Food; Foundations; Genetic; Goals; Horns; Hunger; Institutes; Knowledge; Lateral; Link; Lobe; Logic; Maps; Mediating; Methods; Molecular; Molecular Biology; Molecular Genetics; Motivation; National Institute on Deafness and Other Communication Disorders; Nervous system structure; Neurons; Odorant Receptors; Odors; Olfactory Pathways; Olfactory tract; Organism; Output; Pattern; Peripheral; Pharmacology; Population; Process; Property; Proxy; Quantitative Reverse Transcriptase PCR; Receptor Gene; Reporter; Research; Resolution; Role; Route; Satiation; Sensory; Shapes; Signal Transduction; Smell Perception; Specificity; Starvation; Stereotyping; Stimulus; Synapses; System; Taste Perception; Techniques; Testing; Training; Translations; Vertebrates; Work; behavioral response; dopaminergic neuron; flexibility; fly; genetic manipulation; in vivo; increased appetite; millisecond; neural circuit; neural patterning; neuroregulation; olfactory stimulus; operation; optogenetics; patch clamp; postsynaptic; postsynaptic neurons; receptor; receptor expression; relating to nervous system; response; sensory input; sensory stimulus; spatiotemporal; two photon microscopy; two-photon

Project Summary/Abstract Neurons “encode” sensory stimuli into patterns of electrical activity. This activity is then transformed or “decoded” by downstream neurons to guide behavior. However, in different contexts, the same sensory input can drive different behavioral outputs. For instance, the smell of food can be attractive leading up to a meal, but aversive or neutral right after a meal. While we have an emerging understanding of how peripheral sensory neurons change their encoding, we have almost no understanding of how downstream central neurons decode this information, or how decoding changes with behavioral contexts, such as hunger. The gap in our knowledge about neural decoding exists because it is difficult to identify all the neurons in a population that participate in a code. Additionally, identifying and recording from neurons postsynaptic to that population is usually restrictive. Here, I will overcome these barriers to understanding neural decoding by using the tractable olfactory system of the fruit fly, Drosophila melanogaster. In the fly, 2nd-order projection neurons (PNs, analogous to mitral/tufted cells in vertebrates) form a well-characterized code for odor. 3rd-order neurons called lateral horn neurons (LHNs) receive stereotyped olfactory input from PNs innervating multiple glomeruli. The specific goals of this proposal are to establish how LHNs decode spike patterns from PNs and how neuromodulatory signaling alters this process. I will use 2-photon optogenetics to directly control spike patterns in PNs of multiple glomeruli simultaneously with cellular and <10 msec resolution. I will simultaneously record from identified, postsynaptic LHNs in vivo, to determine what properties of the PN odor code are truly relevant for driving LHN activity. Then, I will incorporate pharmacology and genetic manipulations to identify how dopamine signaling changes how LHNs decode PN activity. Finally, I will use established molecular genetics methods to probe the cellular specificity of hunger-induced changes in dopamine receptor expression to determine how internal state changes the dopaminergic “landscape” in the lateral horn. Altogether, this project will provide fundamental knowledge of how the brain reads and dynamically shapes its own olfactory code at the systems, cellular, and molecular level. This proposal supports my continued interdisciplinary training in in vivo electrophysiology and molecular biology, and provides new training in optogenetics and 2-photon microscopy. Moreover, it addresses NIDCD’s stated priorities to understand the fundamental biology of chemosensory function and the central control of smell.

项目概要/摘要 神经元将感觉刺激“编码”成电活动模式。然后该活动被转化或 由下游神经元“解码”以指导行为。然而，在不同的情境下，相同的感官输入 可以驱动不同的行为输出。例如，吃饭前食物的气味可能很有吸引力， 但饭后立即表现出厌恶或中性。虽然我们对外围感觉如何 神经元改变它们的编码，我们几乎不了解下游中枢神经元如何解码 这些信息，或者解码如何随着行为环境（例如饥饿）而变化。我们的差距 关于神经解码的知识之所以存在，是因为很难识别群体中的所有神经元 参与一个代码。此外，从突触后神经元到该群体的识别和记录是 通常是限制性的。 在这里，我将通过使用易于处理的嗅觉来克服这些理解神经解码的障碍 果蝇系统，果蝇。在飞行中，二阶投影神经元（PN，类似于 脊椎动物的二尖瓣/簇状细胞）形成了良好表征的气味代码。三级神经元称为侧角 神经元 (LHN) 接收来自支配多个肾小球的 PN 的固定嗅觉输入。具体的 该提案的目标是确定 LHN 如何从 PN 中解码尖峰模式以及如何 神经调节信号改变这个过程。我将使用2光子光遗传学来直接控制尖峰 多个肾小球 PN 模式同时具有细胞分辨率和 <10 毫秒分辨率。我会同时 从已识别的体内突触后 LHN 进行记录，以确定 PN 气味代码的真正属性 与推动 LHN 活动相关。然后，我将结合药理学和基因操作来识别 多巴胺信号传导如何改变 LHN 解码 PN 活动的方式。最后，我将使用已建立的分子 遗传学方法探测饥饿引起的多巴胺受体表达变化的细胞特异性 确定内部状态如何改变侧角的多巴胺能“景观”。 总而言之，该项目将提供有关大脑如何阅读和动态阅读的基础知识。 在系统、细胞和分子水平上形成自己的嗅觉密码。这个提案支持我的 继续体内电生理学和分子生物学的跨学科培训，并提供新的 光遗传学和双光子显微镜培训。此外，它还解决了 NIDCD 所声明的优先事项： 了解化学感应功能的基本生物学和气味的中枢控制。