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

基本信息

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
项目类别：
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

项目摘要

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，然后这种活动被转化或转化。由下游神经元“解码”以指导行为然而，在不同的上下文中，相同的感觉输入。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，但饭后立即感到厌恶或中性，而我们对末梢感觉如何产生新的了解。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。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此外，从突触后神经元到该群体的识别和记录也是如此。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，果蝇中的二阶投射神经元（PN，类似于）。脊椎动物的二尖瓣/簇状细胞）形成了一种特征明确的气味代码，称为侧角。神经元 (LHN) 接收来自支配多个肾小球的 PN 的定型嗅觉输入。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。多个肾小球的 PN 模式同时具有细胞分辨率和 <10 毫秒的分辨率。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然后，我将通过药物整合和基因操作来识别。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代码这个提议支持了我的观点。继续体内电生理学和分子生物学的跨学科培训，并提供新的此外，它还解决了 NIDCD 规定的优先事项：了解化学感应功能的基本生物学和嗅觉的中枢控制。