The Receptor Basis for the Neuromodulation of Olfactory Processing by Serotonin

描述（由申请人提供）：我们的大脑必须根据个体当前的生理需求改变处理感觉信息的方式。例如，当我们饥饿时，我们的嗅觉和味觉系统会更加敏锐。为了实现这种灵活性，神经系统依赖于“神经调节剂”的释放，它改变神经元的反应特性，以优化神经系统在适当环境下处理信息的能力。神经调节是神经系统的一个普遍特征，因此许多神经系统疾病，如精神分裂症和抑郁症，都是由神经调节系统功能失调引起的。尽管神经调节对健康的感觉加工很重要，但由于脊椎动物神经系统中表达的神经调节受体类型的多样性（例如，脊椎动物拥有14种血清素受体），我们预测神经调节后果的能力受到限制。在这个应用中，我们建议通过使用一个具有较少受体的模型感觉系统（5个血清素受体，而不是14个）来解决这一知识缺陷，即果蝇的嗅觉系统。本应用程序的目的是确定果蝇嗅觉系统中血清素受体表达的功能模式，以及个体受体对血清素调节感觉输入的贡献。本研究的长期目标是确定不同功能类别的神经元如何表达个体受体，每个受体如何参与神经调节的网络水平效应。在脊椎动物和无脊椎动物的嗅觉系统中，血清素在清醒状态的生理环境中增强了气味诱发的反应。然而，如果不知道表达每种5 -羟色胺受体的神经元的功能特性，就很难确定嗅觉处理的哪些特征是直接改变的，从而导致5 -羟色胺的网络效应。具体目标

DESCRIPTION (provided by applicant): Our brain must alter the way in which it processes sensory information based on the present physiological needs of the individual. For instance, our olfactory and gustatory systems are much more acute when we are hungry. To achieve this flexibility the nervous system relies on the release of "neuromodulators" which alter the response properties of neurons to optimize the ability of the nervous system to process information in the appropriate context. Neuromodulation is a ubiquitous feature of the nervous system and thus many neurological disorders, such as schizophrenia and depression, arise from dysfunctional neuromodulatory systems. Despite the importance of neuromodulation for healthy sensory processing, our ability to predict the consequences of neuromodulation has been limited due to the diversity of neuromodulatory receptor types expressed in the vertebrate nervous system (for instance, vertebrates possess 14 serotonin receptors). In this application, we propose to address this knowledge deficit by using a model sensory system with fewer receptors (5 serotonin receptors as opposed to 14), the olfactory system of Drosophila. The objective of this application is to determine the functional patterns of serotonin receptor expression within the olfactory system of Drosophila and the contribution of individual receptors towards the modulation of sensory input by serotonin. The long-term goal of this research is to determine how individual receptors expressed by distinct functional classes of neurons each contribute to the network level effects of neuromodulation. In the vertebrate and invertebrate olfactory system, serotonin enhances the odor-evoked responses within the physiological context of the waking state. However, without knowing the functional identity of neurons expressing each serotonin receptor, it is very difficult to determine which features of olfactory processing are directly altered resulting in the network-wide effects of serotonin. In Specific Aim 1 we will use immunocytochemistry in combination with genetic tagging to determine the transmitter content of the neurons expressing each of the four serotonin receptor types. To understand the contribution of any given receptor to the network-level effects of a neuromodulator, it is critical to understand the consequences of receptor activation for each functional neuronal type expressing a given receptor. In Specific Aim 2 we will manipulate the expression levels of a single serotonin receptor in a functionally discrete set of sensory neurons and use behavioral assays to determine the extent to which modulation of sensory neuron input by a single serotonin receptor influences olfactory processing.