Mechanisms of flexible neural decoding in the fly olfactory system

项目总结/摘要 神经元将感觉刺激“编码”成电活动的模式。然后，该活动被转换或 由下游神经元“解码”以指导行为。然而，在不同的语境中，同样的感官输入 可以驱动不同的行为输出。例如，食物的气味可能是有吸引力的导致一顿饭， 但在饭后是厌恶或中性的。虽然我们对外周感觉如何 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（如饥饿）而变化。我们之间的差距 存在关于神经解码的知识是因为很难识别 参与一个代码。此外，识别和记录突触后神经元到该群体是非常重要的。 通常限制性。 在这里，我将克服这些障碍，通过使用易处理的嗅觉来理解神经解码。 黑腹果蝇（Drosophila melanogaster）。在果蝇中，二阶投射神经元（PN，类似于 脊椎动物中的僧帽细胞/簇状细胞）形成了一种良好表征的气味代码。第三阶神经元称为侧角 神经元（LHN）从支配多个肾小球的PN接收刻板的嗅觉输入。具体 该建议的目标是确定LHNs如何从PN解码尖峰模式，以及如何 神经调节信号改变了这一过程。我会用双光子光遗传学直接控制spike 同时具有细胞和<10 msec分辨率的多个肾小球的PN模式。我将同时 记录从识别，突触后LHN在体内，以确定什么属性的PN气味代码是真正的 与驱动LHN活动相关。然后，我将结合药理学和基因操作，以确定 多巴胺信号传导如何改变LHN解码PN活性的方式。最后，我将使用已建立的分子 用遗传学方法探测饥饿诱导多巴胺受体表达变化的细胞特异性 以确定内部状态如何改变侧角的多巴胺能“景观”。 总而言之，这个项目将提供大脑如何阅读和动态阅读的基本知识。 在系统、细胞和分子水平上形成自己的嗅觉密码。这项建议支持我的 继续在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的培训。此外，它还述及防治荒漠化全国委员会所述的优先事项， 了解化学感觉功能的基本生物学和嗅觉的中枢控制。

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.