State-Dependent Olfactory Information Processing

项目摘要 感觉知觉，意识到刺激，根据大脑状态而变化。在睡眠中，人们无法 感知许多感官刺激，他们会在清醒时，一个过程被称为状态， 依赖性感觉门控大多数感觉方式依赖于丘脑在睡眠期间充当感觉门; 然而，嗅觉信息可以在没有丘脑中继的情况下到达皮层，这使得人们不清楚嗅觉信息是如何传递的。 嗅觉系统实现感觉门控。气味感知始于气味物质与嗅觉的结合 感觉神经元（OSN）在鼻子，然后投射到嗅球（OB）。来自产科，嗅觉 信息被传递到嗅觉皮层（包括梨状皮层，PC），然后到眶额 皮质（OFC）。在这个建议中，我们将使用光遗传学，电生理学和自然气味刺激， 自由行为的老鼠，以了解啮齿动物的嗅觉系统是如何能够门的感觉信息。 初步研究表明，嗅觉信息可以在睡眠期间到达大脑皮层而不会衰减， 通过睡眠期间较大的诱发局部场电位（LFP）幅度来测量。此外，还有一个 在清醒而非睡眠期间刺激后伽马振荡增加。我们假设感官 反应（除了伽马振荡）在睡眠期间大部分保存在嗅觉皮层中， 减少了对OB的自上而下的皮层输入，其主要功能是通过增强 局部抑制我们将从两个方面来检验这一假设。在目标1中，在自然睡眠和清醒状态期间， 将从多个嗅觉区域同时记录，并将在 前PC响应于光遗传学刺激和递送的天然气味刺激 以避免在不同的大脑状态下改变呼吸的混乱。目标2： 进一步了解OB局部抑制在这一过程中的作用，而不是激活多种OSN类型 (ie通过光遗传学刺激，单个肾小球将被刺激以使效应最小化 侧抑制。此外，将在麻醉下进行记录，以使该结果与 以前对这个问题的研究。这些实验将揭示嗅觉信息的差异 在自然睡眠/清醒状态下进行处理，并为这些差异提供机制。

Project Summary Sensory perception, being aware of a stimulus, varies depending on brain state. During sleep, individuals fail to perceive many of the sensory stimuli that they would during wakefulness, a process referred to as state- dependent sensory gating. Most sensory modalities rely on the thalamus to act as a sensory gate during sleep; however, olfactory information can reach the cortex without the relay of the thalamus making it unclear how the olfactory system achieves sensory gating. Odor perception begins with the binding of odorants to the olfactory sensory neurons (OSNs) in the nose, which then project to the olfactory bulb (OB). From the OB, olfactory information is transmitted to the olfactory cortices (including the piriform cortex, PC) then to the orbitofrontal cortex (OFC). In this proposal, we will use optogenetics, electrophysiology, and natural odor stimulation in freely behaving mice to understand how the rodent olfactory system is able to gate sensory information. Preliminary studies suggest that olfactory information can reach the cortex without attenuation during sleep, as measured by larger evoked local field potential (LFP) amplitudes during sleep. Additionally, there is an increase in gamma oscillations following stimulation during wake but not sleep. We hypothesize that sensory responses (except for gamma oscillations) are largely preserved in olfactory cortices during sleep due to reduced top-down cortical inputs to the OB, which primarily function to decrease OB outputs by enhancing local inhibition. We will test this hypothesis in two aims. In Aim 1, during natural sleep and wake states, LFPs will be recorded simultaneously from multiple olfactory regions and single-unit recordings will be performed in the anterior PC in response to both an optogenetic stimulation and a natural odor stimulation that is delivered into the nasal cavity as to avoid the confounds of changed breathing in different brain states. In Aim 2, to further understand the role of the OB local inhibition in this process, instead of activating multiple OSN types (ie multiple glomeruli) by optogenetic stimulation, a single glomerulus will be stimulated to minimize the effect of lateral inhibition. Additionally, recordings will be performed under anesthesia to reconcile this result with previous studies on this topic. Together, these experiments will reveal the differences in olfactory information processing in natural sleep/wake states and provide a mechanism for these differences.