Cholinergic modulation of olfactory coding.

嗅觉编码的胆碱能调节。

• 批准号: 10442217
• 负责人: MAX L FLETCHER
• 金额: $ 46.54万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10442217
• 关键词: Acetylcholine; Address; Affect; Alzheimer' s Disease; Animals; Behavior; Behavioral; Behavioral Assay; Brain; Brain region; Calcium; Cells; Characteristics; Cholinergic Fibers; Cholinergic Receptors; Code; DDX26 gene; Data; Detection; Diagnosis; Discrimination; Disease; Event; Fiber; Goals; Head; Human; Image; Impaired cognition; Knowledge; Lead; Learning; Mediating; Mus; Neurons; Odors; Olfactory Pathways; Olfactory dysfunction; Output; Parkinson Disease; Perception; Pharmacology; Physiological; Play; Population; Process; Receptor Activation; Role; Sensory; Signal Transduction; Smell Perception; Stimulus; Structure; System; Testing; Work; awake; basal forebrain; basal forebrain cholinergic neurons; base; behavioral study; calcium indicator; cell type; cholinergic; cholinergic neuron; experimental study; improved; in vivo; insight; microendoscope; nervous system disorder; neural circuit; neuronal circuitry; novel; olfactory bulb; piriform cortex; response; sensory discrimination; sensory input; two-photon

Project Summary Understanding how brain states influence sensory coding is fundamental in advancing our knowledge of the mechanisms by which neural circuits encode sensory information. The basal forebrain cholinergic system has long been implicated in such state changes and has been shown to play a crucial role in the detection, selection, and processing of behaviorally relevant stimuli. However, to date, almost all work regarding cholinergic modulation of olfactory circuits has focused on the effects of acetylcholine on olfactory system neurons while largely ignoring the circumstances that drive cholinergic neuron activity. Thus, very little is currently known regarding the conditions that drive basal forebrain cholinergic neuron activity or the characteristics of cholinergic fiber activity within the olfactory bulb. Further, fundamental questions also remain regarding the primary function of ACh release on olfactory coding, as most prior studies have focused on olfactory responses in anesthetized mice. For example, in the olfactory bulb, acetylcholine release is thought to enhance the sensitivity of olfactory bulb output cell odor responses and lead to improved olfactory discrimination. However, no experiments have been performed directly addressing these hypothesized functions in awake animals, leaving acetylcholine’s ultimate function within early olfactory regions unknown. The overall goal of this project is to understand this process by investigating how sensory input, stimulus novelty, and odor discrimination drive olfactory projecting cholinergic neuron activity and how this impacts olfactory odor responses. Our central hypothesis is that olfactory projecting cholinergic neurons preferentially respond to novel stimuli and impart information regarding salience to the olfactory circuits. We will use calcium imaging of defined cholinergic and olfactory system cell types combined with chemogenetic manipulation in awake animals during well-characterized olfactory-mediated behaviors to test this hypothesis. The findings of these experiments will be significant in that they will fundamentally advance our knowledge of the function of cholinergic input during olfactory-related events, how this affects sensory representations at multiple levels within the olfactory system, and how this ultimately impacts olfactory perception and discrimination.

项目摘要 了解大脑状态如何影响感觉编码是推进我们对大脑的认知的基础。 神经回路编码感官信息的机制。基底前脑胆碱能系统 长期以来一直与这种状态变化有关，并已被证明在检测，选择， 和行为相关刺激的处理。然而，到目前为止，几乎所有关于胆碱能的工作， 嗅觉回路的调节集中在乙酰胆碱对嗅觉系统神经元的影响， 很大程度上忽略了驱动胆碱能神经元活动的环境。因此，目前所知甚少 关于驱动基底前脑胆碱能神经元活动的条件或胆碱能神经元的特征， 嗅球内的纤维活动。此外，关于主要功能的基本问题也仍然存在， 乙酰胆碱释放对嗅觉编码的影响，因为大多数先前的研究都集中在麻醉后的嗅觉反应上， 小鼠例如，在嗅球中，乙酰胆碱的释放被认为可以增强嗅觉的敏感性。 灯泡输出细胞的气味反应，并导致改善嗅觉辨别。然而，没有任何实验 在清醒的动物中直接进行这些假设的功能，留下乙酰胆碱的 早期嗅觉区的最终功能未知。本项目的总体目标是了解这一点 通过研究感觉输入、刺激新奇性和气味辨别如何驱动嗅觉投射来进行过程 胆碱能神经元的活动以及这如何影响嗅觉气味反应。我们的中心假设是嗅觉 投射胆碱能神经元优先对新的刺激作出反应，并传递关于显著性的信息 到嗅觉回路我们将使用钙成像确定胆碱能和嗅觉系统细胞类型 在清醒的动物中结合化学发生学操作， 行为来检验这个假设。这些实验的结果将是重要的，因为它们将 从根本上推进我们对胆碱能输入在嗅觉相关事件中的功能的认识， 这会影响嗅觉系统中多个层次的感觉表征，以及这最终如何影响 嗅觉和辨别力。