Basal Forebrain Modulation of Olfactory Bulb Function

嗅球功能的基础前脑调节

• 批准号: 10456633
• 负责人: ADAM C PUCHE
• 金额: $ 63.05万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456633
• 关键词: Address; Affect; Alzheimer' s Disease; Animal Behavior; Animals; Area; Attention; Axon; Behavior; Behavioral; Brain; Brain region; Cell Nucleus; Cells; Cognition; Cues; Data; Decision Making; Diagonal Band Nucleus; Discrimination; Eating; Electrophysiology (science); Funding; Goals; Image; In Vitro; Investigation; Lateral; Learning; Link; Mediating; Modality; Mus; Neocortex; Neurons; Odors; Olfactory Pathways; Olfactory tract; Output; Pattern; Pharmacogenetics; Pharmacology; Play; Population; Prosencephalon; Reporter; Resolution; Rewards; Rodent; Role; Sensory; Signal Transduction; Site; Slice; Smell Perception; Structure; Testing; alertness; attentional modulation; awake; basal forebrain; behavioral response; cell type; cholinergic; cognitive function; driving behavior; in vivo; in vivo imaging; information processing; inhibitory neuron; learned behavior; microendoscopy; multidisciplinary; neural circuit; neurochemistry; neuroregulation; novel; olfactory bulb; optogenetics; patch clamp; response; sensory input; sensory system; tool

PROJECT SUMMARY Sensory systems, including olfaction, are heavily dependent on signals from higher brain regions that regulate behavioral states of alertness and attention. A major center for these modulatory inputs is the basal forebrain. The basal forebrain (BF) sends axonal projections throughout the brain and has been implicated in dynamic modulation of cortical as well as sensory circuits during behavior. BF is classically thought of as a center for cholinergic projections throughout the brain, whose chief functional role is to mediate attentional modulation of information processing. However, the recent advent of novel tools for probing neural circuits in vivo has enabled a deeper and more nuanced understanding of basal forebrain organization and role in cognition. BF projections to neocortex are in fact neurochemically diverse and precisely organized with respect to projection target. Further, different BF subpopulations are linked to distinct aspects of behavior and are implicated in diverse cognitive functions including reward signaling, behavioral responding to sensory cues and task learning. Despite these advances, however, we still know little about BF impact on the initial processing of sensory inputs on their way to cortex. The olfactory bulb (OB) is advantageous for investigating basal forebrain function, as it is the only primary (pre-cortical) sensory processing area receiving BF inputs and because olfaction is a primary modality driving behavior in rodents. BF sends massive projections to the OB, with terminations in all OB layers. Many of these projections are cholinergic. However, as for neocortex, BF projections to OB are neurochemically diverse with substantial numbers of GABAergic neurons. The importance of this diversity has only recently begun to be appreciated for cortex, but almost entirely unexamined with respect to OB circuitry. A recent study showed that GABAergic basal forebrain projections to the olfactory bulb target distinct neuronal subpopulations and can, independent of cholinergic projections, modulate OB circuits to affect odor perception. However, our understanding of the respective roles played by BF cholinergic and GABAergic in modulating OB circuits and odor perception remains rudimentary. Fundamental unanswered questions include whether cholinergic and GABAergic basal forebrain projections target distinct components of olfactory bulb circuits, whether they have complementary or opposing effects on odor representations at the level of olfactory bulb output, what are the activity patterns of cholinergic and GABAergic basal forebrain neurons during behavior, and what role these projections play in odor perception or odor-guided behaviors? The overall goal of this proposal is to investigate how the basal forebrain neuromodulatory inputs affect olfactory bulb function in a multi-disciplinary study spanning investigation at the level of single neurons through to animal behavior utilizing advances in electrophysiology, opto-/pharmacogenetics, and high resolution activity imaging and microendcosopy in behaving animals.

项目总结 感觉系统，包括嗅觉，严重依赖于来自大脑高级区域的信号，这些区域 调节警觉和注意力的行为状态。这些调节输入的一个主要中枢是基底节 前脑。基底前脑(BF)在整个大脑中发送轴突投射，并与 行为过程中大脑皮层和感觉回路的动态调节。高炉被经典地认为是一种 整个大脑的胆碱能投射中心，其主要功能是调节注意力 信息处理的调制。然而，最近出现的用于探测神经电路的新工具 VIVO使我们能够更深入和更细微地了解基础前脑的组织和作用 认知力。事实上，BF对新皮质的投射在神经化学上是多样化的，并且是按照尊重 投射目标。此外，不同的BF亚群与行为的不同方面有关，并且是 涉及不同的认知功能，包括奖励信号，对感觉提示的行为反应和 任务学习。然而，尽管有这些进展，我们仍然对高炉在初始加工过程中的影响知之甚少。 感觉输入进入大脑皮层。 嗅球(OB)是研究基底前脑功能的唯一初级脑区。 (皮层前)感觉处理区，接受BF输入，因为嗅觉是主要的驱动方式 啮齿动物的行为。BF向OB发送大量投影，并在所有OB层终止。其中许多 投射是胆碱能的。然而，对于新皮质，BF向OB的投射在神经化学上是不同的， 大量的GABA能神经元。这种多样性的重要性直到最近才开始 对于皮层很欣赏，但几乎完全没有关于OB电路的检查。最近的一项研究表明， GABA能基底前脑向嗅球投射靶向不同的神经元亚群， 独立于胆碱能投射，调节OB回路以影响气味感觉。然而，我们的 了解BF胆碱能和GABA能在调节OB回路和 气味感知仍处于初级状态。基本悬而未决的问题包括胆碱能和 GABA能基底前脑投射靶向嗅球回路的不同组件，无论它们是否有 在嗅球输出水平上对气味表征的互补或相反的影响是什么？ 行为过程中胆碱能和GABA能基底前脑神经元的活动模式，以及这些活动在行为中的作用 投射在气味感知或气味引导行为中起作用？ 这项提议的总体目标是研究基底前脑神经调节输入如何影响 嗅球功能在一项多学科研究中的应用，该研究跨越单个神经元水平，通过 利用电生理学、光/药物遗传学和高分辨活性的进展对动物行为的影响 行为动物的成像和显微内窥镜。