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: 10579330
• 负责人: Kristyn Lizbinski
• 金额: $ 7.63万
• 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/10579330
• 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.

项目总结/文摘