Synaptic modulation in neural circuits

描述（由申请人提供）：在一个充满竞争信息的环境中，动物面临着检测对其生存和繁殖成功至关重要的刺激的挑战。中心-环绕、方向选择性和颜色对立等神经机制促进了早期视觉系统的特征提取。然而，对于嗅觉系统中感知显著性是如何实现的，人们知之甚少。我们假设突触调节的增益控制是一种重要的机制，可以减少不相关的嗅觉信息，并加强神经对环境中行为相关线索的反应。在动物王国中，包括昆虫和哺乳动物在内的许多物种的嗅觉系统都表现出类似的设计原理。昆虫气味受体神经元（orn）将气味信息传递到触角叶（AL）的肾小球，触角叶是一种类似脊椎动物嗅球的结构。天线叶的兴奋性和抑制性局部中间神经元（LNs）在控制天线叶输出中起重要作用。二级投射神经元（PNs）的轴突支配着两个较高的脑中枢——蘑菇体（MB）和侧角（LH）。解剖学上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特征提取的神经回路的系统。目的1的实验旨在探讨多巴胺在情境依赖嗅觉行为中的调节机制。在目标2和目标3中，我们将检验血清素（一种与觉醒和清醒相关的神经调节剂）在嘈杂气味环境中促进对比度增强和增强功能的假设。行为实验旨在测试血清素在这种情况下的作用（具体目标2）。生理实验旨在更好地了解天线叶回路介导血清素对气味表征的影响（Specific Aim 3）。神经调节剂在响应内部和外部线索灵活改变局部电路突触加工中发挥关键作用。提议的项目解决了5 -羟色胺和多巴胺在嗅觉处理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嗅觉回路中发挥作用的基本原理，将有助于了解针对血清素或多巴胺信号的不同治疗药物如何影响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.