Cholinergic modulation of olfactory coding.

项目摘要 了解大脑状态是如何影响感觉编码的，是推进我们对 神经回路编码感觉信息的机制。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 嗅路的调制主要集中在乙酰胆碱对嗅觉系统神经元的影响，而 很大程度上忽略了驱动胆碱能神经元活动的环境。因此，目前所知的很少。 关于驱动基底前脑胆碱能神经元活动的条件或胆碱能特征 嗅球内的纤维活动。此外，关于主要职能的基本问题也依然存在。 ACh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 老鼠。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，没有一项实验表明 在清醒的动物身上直接解决了这些假设的功能，留下了乙酰胆碱 早期嗅觉区域的终极功能未知。本项目的总体目标就是理解这一点 通过研究感觉输入、刺激新颖性和气味辨别如何驱动嗅觉投射的过程 胆碱能神经元活动及其对嗅觉反应的影响。我们的中心假设是嗅觉 投射胆碱能神经元优先对新刺激作出反应并传递有关突显的信息 传到嗅觉回路。我们将使用确定的胆碱能和嗅觉系统细胞类型的钙成像 在具有良好特性的嗅觉介导的清醒动物中结合化学遗传操作 来检验这一假设的行为。这些实验的发现将具有重要意义，因为它们将 从根本上提高我们对胆碱能输入在嗅觉相关事件中的作用的了解，如何 这会影响嗅觉系统内多个层次的感觉表征，以及最终如何影响 嗅觉和辨别能力。

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.