Synaptic modulation in neural circuits

描述(申请人提供)：在一个充斥着相互竞争的信息的环境中，动物面临着检测对它们的生存和繁殖成功至关重要的刺激的挑战。在早期视觉系统中，中心-周围、方位选择性和颜色对抗性等神经机制促进了特征提取。然而，对于嗅觉系统中知觉的显着性是如何实现的，人们知之甚少。我们假设，通过突触调节获得控制是修剪无关嗅觉信息和加强神经对环境中行为相关线索的反应的重要机制。嗅觉系统在动物界的许多物种中都表现出类似的设计原则，包括昆虫和哺乳动物。昆虫气味感受器神经元(ONS)将气味信息传递到触角叶(AL)的肾小球，触角叶的结构类似于脊椎动物的嗅球。触角叶中的兴奋性和抑制性局部中间神经元在控制触角叶输出方面起着重要作用。二级投射神经元(PNS)的轴突支配两个较高级的脑中枢--蘑菇体(MB)和侧角(LH)。解剖的简单性和遗传学的力量使果蝇成为一个特别适合研究嗅觉系统中特征提取的神经回路的系统。AIMS 1中的实验旨在探索多巴胺在上下文相关嗅觉行为中的调制机制。在目标2和目标3中，我们将测试这一假设，即5-羟色胺是一种与觉醒和觉醒相关的神经调节剂，它促进对比度增强，并在嘈杂的气味环境中增强功能。行为实验的目的是测试5-羟色胺在这方面的作用(具体目标2)。生理学实验是为了更好地理解5-羟色胺对气味表现的影响的触角叶回路(具体目标3)。神经调节剂在灵活地改变局部回路中突触的处理过程中发挥关键作用，以响应内部和外部提示。这些拟议的项目解决了5-羟色胺和多巴胺在嗅觉处理中的一个基本问题中的作用：嗅觉环境如何影响某些嗅觉特征的显着性？了解神经调节剂如何在简单的嗅觉回路上发挥作用的基本原理，将有助于理解不同的靶向5-羟色胺或多巴胺信号的治疗剂如何塑造神经系统中的信息处理。

DESCRIPTION (provided by applicant): In an environment cluttered with competing information, animals are faced with the challenge of detecting stimuli critical for their survival and reproductive success. Neural mechanisms such as center-surround, orientation selectivity and color opponency promote feature extraction in the early visual system. Less is understood, however, about how perceptual saliency is achieved in the olfactory system. We hypothesize that gain control by synaptic modulation is an important mechanism to prune irrelevant olfactory information and accentuate neural response to behaviorally relevant cues in the environment. Olfactory systems exhibit similar design principles across many species in the animal kingdom, including insects and mammals. Insect odorant receptor neurons (ORNs) relay odor information to glomeruli in the antennal lobe (AL), a structure that resembles the vertebrate olfactory bulb. Excitatory and inhibitory local interneurons (LNs) in the antennal lobe play an important role in controlling antennal lobe output. Axons of second order projection neurons (PNs) innervate two higher brain centers - the mushroom body (MB) and the lateral horn (LH). The anatomical simplicity and the power of genetics make Drosophila a particularly amenable system to study the neural circuit for feature extraction in the olfactory system. Experiments in Aims 1 are designed to probe the modulatory mechanism of dopamine in a context-dependent olfactory behavior. In Aims 2 and 3, we will test the hypothesis that serotonin, a neuromodulator associated with arousal and wakefulness, promotes contrast enhancement and functions to enhance feature in a noisy odor environment. Behavioral experiments are aimed to test the role of serotonin in this context (Specific Aim 2). Physiological experiments are designed to better understand the antennal lobe circuitry mediating serotonin's effects on odor representation (Specific Aim 3). Neuromodulators play key roles in flexibly altering synaptic processing in local circuits in response to both internal and external cues. The proposed projects address the role of serotonin and dopamine in a fundamental problem in olfactory processing: how does olfactory context influence the saliency of certain olfactory features? Understanding basic principles about how neuromodulators exert their actions on simple olfactory circuits will provide insight into understanding how different therapeutic agents targeting serotonin or dopamine signaling shape information processing in neural systems.