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个中继，触角叶的转换。阐明信息如何在层级系统中传播是理解感觉编码机制的重要一步。嗅觉编码是揭示感觉回路如何产生、传播和读取神经代码以创建感觉感知的有用模型。昆虫的嗅觉系统是一个易于理解的系统，用于解释感觉处理机制，因为它们比哺乳动物用更简单的电路实现气味辨别。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件。在一组初步的实验中，我们发现了果蝇嗅觉受体神经元GABAB调制的解剖学和生理学证据。我们发现受体提供了一种机制，以扩大系统的动态范围，令人惊讶的是，我们发现，突触前抑制的水平是异质性的输入通道之间。我们假设，GABAB在选择神经元的表达提供了一种机制，嗅觉输入的行为相关的反馈调制。我们提出了一组实验，以进一步研究反馈抑制的分子，生理和行为水平上的机制。我们使用分子技术来表征受体的表达，并使用钙离子和突触荧光素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。这些结果将为嗅觉系统中感觉输入的调节提供新的见解，并且这些发现可以为反馈抑制在检测行为相关线索中的功能提供新的见解。 与公共卫生的相关性。阐明感官知觉的机制对于理解感觉系统在正常情况下和疾病中的功能至关重要。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，并且在其他动物中更难的尖端科学中具有强大的分子工具。这项提案的工作是基础科学，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奠定知识基础。这样的工作可能会揭示适用于更大的更复杂的电路和神经功能的感觉系统的神经障碍相关的基本电路特性。

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.