Fine tuning odor representation by presynaptic inhibition of receptor neurons

描述(申请人提供)：这项工作的目的是阐明在果蝇大脑的第一个中继器，触角叶中嗅觉信息的转换。阐明信息如何在等级系统中传播是理解感觉编码机制的重要一步。嗅觉编码是一个有用的模型，可以用来揭示感觉回路是如何产生、传播和读取神经编码来创造感觉的。昆虫嗅觉系统是破译感觉处理机制的一个容易处理的系统，因为它们比哺乳动物用更简单的电路实现气味识别。此外，果蝇提供了一套强大的分子工具，可以用来操纵潜在电路的个别元素。在一系列初步的实验中，我们发现了GABAB调节果蝇嗅觉感受器神经元的解剖学和生理学证据。我们发现受体提供了一种机制来扩大系统的动态范围，令人惊讶的是，我们发现突触前抑制水平在输入通道之间是不同的。我们假设，GABAB在特定神经元中的表达为嗅觉输入的行为相关反馈调制提供了一种机制。我们提出了一系列实验，从分子、生理和行为水平进一步研究反馈抑制的机制。我们使用分子技术来表征受体的表达，并使用钙和突触Hluorin的双光子成像来监测突触前活动和突触传递。我们将检验反馈抑制为嗅觉适应和动态范围扩展提供机制的假设。这一结果将为嗅觉系统中感觉输入的调节提供新的见解，并为反馈抑制在行为相关线索的检测中的作用提供新的见解。 与公共卫生的相关性。阐明感觉知觉的机制对于理解感觉系统如何正常和在疾病中发挥作用至关重要。我们研究苍蝇嗅觉系统中感觉输入信号的调制，因为它相对简单，并且有一套强大的分子工具用于尖端科学，而这在其他动物中更难。这项提议的工作是一门基础科学，旨在揭示有关感觉神经系统的基本原理，为未来的医学和技术研究创造一个知识库。这样的工作可能揭示出适用于更大、更复杂的电路和神经功能的基本电路特性，这些电路和神经功能与感觉系统的神经紊乱有关。

DESCRIPTION (provided by applicant): The purpose of this work is to elucidate the transformation of olfactory information in the first relay of the Drosophila brain, the antennal lobe. Elucidating how information propagates in a hierarchical system is an important step towards understanding sensory coding mechanisms. Olfactory coding is a useful model for revealing how sensory circuits generate, propagate and read a neural code to create sensory perception. The insect olfactory system is a tractable system for deciphering mechanisms of sensory processing because they achieve odor discrimination with simpler circuits than that of mammals. Furthermore, Drosophila offers a powerful set of molecular tools available to manipulate individual elements of the underlying circuit. In a preliminary set of experiments, we have found anatomical and physiological evidence for GABAB modulation of olfactory receptor neurons in Drosophila. We find the receptor provides a mechanism to extend the dynamic range of the system, and surprisingly we find that level of presynaptic inhibition is heterogeneous between input channels. We hypothesize that GABAB expression in select neurons provides a mechanism for behaviorally relevant feedback modulation of olfactory input. We propose a set of experiments to further investigate the mechanism of feedback inhibition on a molecular, physiological and behavioral level. We use molecular techniques to characterize the receptor expression, and two-photon imaging of calcium and synaptopHluorin to monitor presynaptic activity and synaptic transmission. We will test the hypothesis that feedback inhibition provides a mechanism for olfactory adaptation and dynamic range expansion. The results will provide new insight into modulation of sensory input in the olfactory system and the findings could provide new insight into the function of feedback inhibition in detection of behaviorally relevant cues. Relevance to public health. Elucidating mechanisms of sensory perception is pivotal to understanding how sensory systems function normally and in disease. We study modulation of the sensory input signal in the fly olfactory system because of its relative simplicity and the powerful set of molecular tools for cutting edge science that is more difficult in other animals. The work of this proposal is basic science that seeks to reveal basic principles about the sensory nervous system creating a knowledge base from which future medical and technical research can stem. Such work may reveal fundamental circuit properties applicable to larger more complex circuits and neural functions that are relevant to neurological disorders of sensory systems.