Fine tuning odor representation by presynaptic inhibition of receptor neurons

描述（由申请人提供）：这项工作的目的是阐明嗅觉信息在果蝇大脑的第一中继——触角叶中的转换。阐明信息如何在层次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，它揭示了感觉回路是如何产生、传播和读取神经编码以产生感官知觉的。昆虫的嗅觉系统是一种易于处理的系统，用于破译感觉处理机制，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，可用于操纵底层电路的单个元素。在一组初步的实验中，我们已经发现了GABAB调节果蝇嗅觉受体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展系统的动态范围，令人惊讶的是，我们发现突触前抑制的水平在输入通道之间是不均匀的。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节提供了一种机制。我们提出了一套实验来进一步研究反馈抑制在分子、生理和行为水平上的机制。我们使用分子技术来表征受体表达，并使用钙和突触氟的双光子成像来监测突触前活动和突触传递。我们将验证反馈抑制提供嗅觉适应和动态范围扩展机制的假设。研究结果将为嗅觉系统中感觉输入的调节提供新的认识，并为反馈抑制在行为相关线索检测中的作用提供新的认识。

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.