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: 10730850
• 负责人: Kristyn Lizbinski
• 金额: $ 0.25万
• 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/10730850
• 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; Genetic; Goals; Horns; Hunger; Knowledge; Lateral; Link; Lobe; Logic; Maps; Mediating; Methods; Molecular; Molecular Biology; Molecular Genetics; Motivation; National Institute on Deafness and Other Communication Disorders; Nervous System; Neurons; Odorant Receptors; Odors; Olfactory Pathways; Organism; Output; Pattern; Peripheral; Pharmacology; Population; Process; Property; Proxy; Quantitative Reverse Transcriptase PCR; Receptor Gene; Reporter; Research; Resolution; Role; 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; neural circuit; neural patterning; neuroregulation; olfactory stimulus; operation; optogenetics; patch clamp; postsynaptic; postsynaptic neurons; receptor; receptor expression; 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.

项目摘要/摘要 神经元将感觉刺激“编码”到电活动的模式中。然后转换此活动或 下游神经元“解码”以指导行为。但是，在不同的情况下，相同的感觉输入 可以驱动不同的行为输出。例如，食物的气味可能会吸引一顿饭， 但是饭后厌恶或中立。虽然我们对外围感觉如何有所了解 神经元改变了它们的编码，我们几乎不了解下游中心神经元如何解码 这些信息，或解码如何随饥饿等行为环境而变化。我们的差距 存在有关神经编码的知识，因为很难识别人群中的所有神经元 参与代码。另外，从突触后对该人群的神经元识别和记录是 通常是限制性的。 在这里，我将克服这些障碍来通过使用可拖动的嗅觉来理解神经解码 果蝇的系统，果蝇Melanogaster。在苍蝇中，二阶投射神经元（PNS，类似于 脊椎动物中的二尖瓣/簇状细胞）形成了一种良好的气味代码。三阶神经元称为侧角 神经元（LHNS）从PNS接收刻板的嗅觉输入，这些嗅觉输入了多个肾小球。具体 该建议的目标是确定LHNS如何解码PNS的尖峰模式以及如何解释 神经调节信号传导改变了这一过程。我将使用2片光遗传学直接控制尖峰 具有细胞和<10毫秒分辨率的多个肾小球的PN中的模式。我会很容易 从识别出的，突触后的LHNS在体内的记录，以确定真正的PN气味代码的属性 与驱动LHN活动有关。然后，我将结合药理学和遗传操作以识别 多巴胺信号如何改变LHNS解码PN活性的方式。最后，我将使用已建立的分子 探测饥饿诱导的多巴胺受体表达变化的细胞特异性的遗传学方法 为了确定内部状态如何改变侧角中的多巴胺能“景观”。 总之，该项目将提供有关大脑如何读取和动态读取的基本知识 在系统，细胞和分子水平上塑造其自己的嗅觉代码。该建议支持我 继续进行体内电生理学和分子生物学的跨学科培训，并提供了新的 光遗传学和2光子显微镜的培训。此外，它解决了NIDCD的优先事项 了解化学感应功能的基本生物学和气味的中心控制。