AMINERGIC MODULATION UNDERLYING OLFACTORY PLASTICITY

描述（由申请人提供）：初级感觉神经丸执行环境中复杂感觉信号的初始分解。除了这个基本功能，感觉回路还必须在各种不同的环境条件下区分感知对象，包括可能涉及与其他感觉线索形成习得关联的情况。为了更好地了解帮助稳定大脑内部感知状态的机制，我们需要更彻底地了解来自其他大脑区域的输入是如何调节感觉网络的。对感觉回路的可塑性进行更深入的分析，对于开发更有效的治疗大脑感觉障碍的方法和治疗经常伴随精神疾病的异常感觉至关重要。利用实验上有利的嗅觉系统模型，我们现在有证据表明，基于学习的气味诱发网络反应重组发生在触角叶，结构和功能上类似于哺乳动物的嗅球。嗅觉中枢这种意想不到的网络可塑性背后的机制是什么？为了理解这种调节的本质，研究必须集中在表现这些变化的嗅觉回路的结构和功能组织上，并且必须更多地了解多种神经递质系统之间复杂的相互作用，这些相互作用有助于通过经验重塑嗅觉刺激的时空表征。在曼都卡，四种候选胺递质已经定位于触角叶肾小球的分离神经元，使其成为研究生物胺在嗅觉信息编码中的调节作用的理想系统。该项目将建立在这个实验有利模型的坚实基础上，并将寻求表征嗅觉调节过程中胺能调节在重塑气味表征中的调节作用。我们将采用强大的多学科方法，结合单单元和神经系统记录和解剖学，神经药理学和行为生物测定来研究胺在调节条件作用过程中工厂记忆的形成，储存和回忆中的作用。我们对嗅觉可塑性在早期嗅觉加工中的功能意义的理解仍处于初级阶段，本研究旨在验证离心胺能调节在嗅觉可塑性和适应性行为调节中起关键作用的假设。

DESCRIPTION (provided by applicant): Primary sensory neuropils perform the initial decomposition of complex sensory signals in the environment. Beyond this basic function, sensory circuits also must discriminate perceptual objects under a wide range of different ambient conditions, including situations that may involve the formation of learned associations with other sensory cues. We need a more thorough understanding of how sensory networks are modulated by inputs from other brain regions in order to gain better insight into the mechanisms that help stabilize internal perceptual states in the brain. A deeper analysis of sensory-circuit plasticity is crucial for the development of more effective therapies for sensory brain disorders and treatments for the aberrant sensations that often accompany mental illness. Using the olfactory system of an experimentally favorable model, Manduca Sexta, we now have evidence that a learning-based reorganization of odor-evoked network responses takes place in the antennal lobe, the structural and functional analog of the mammalian olfactory bulb. What mechanisms underlie this unexpected network plasticity in the pdmary olfactory center? In order to understand the nature of this modulation, research must be focused on the structural and functional organization of the olfactory circuits that exhibit these changes, and more must be learned about the complex interplay among multiple neurotransmitter systems that helps to reshape the spatiotemporal representations of olfactory stimuli with experience. In Manduca, four candidate amine transmitters have been localized to separate neurons in the glomeruli of the antennal lobe, making this an ideal system to examine the modulatory roles of biogenic amines in olfactory-information coding. This project will build on a strong foundation of experience with this experimentally-favorable model and will seek to characterize the regulatory roles of aminergic modulation in reshaping odor representations during olfactory conditioning. We will employ a strongly multidisciplinary approach, combining single-unit and neural-ensemble recording & anatomy with neuropharmacology and behavioral bioassays to study the roles of amines in regulating the formation, storage, and recall of offactory memories during the conditioning process. Our understanding of the functional meaning of plasticity in early olfactory processing is still rudimentary, and the proposed studies aim to test the hypothesis that centrifugal aminergic modulation plays a key role in olfactory plasticity and the regulation of adaptive behavior.