State-Dependent Olfactory Information Processing

项目摘要 感知刺激的感觉会因大脑状态的不同而有所不同。在睡眠中，个体无法 感知许多感觉刺激，就像他们在清醒时会感觉到的那样，这个过程被称为状态- 依赖感觉门控。大多数感觉形式依赖于丘脑在睡眠时充当感觉门； 然而，嗅觉信息可以在没有丘脑传递的情况下到达大脑皮层，这使得我们不清楚 嗅觉系统实现了感觉门控。气味感知始于气味与嗅觉的结合 鼻子中的感觉神经元(OSNs)，然后投射到嗅球(OB)。来自OB，嗅觉 信息被传输到嗅皮层(包括梨状皮质，PC)，然后传输到眶前叶 皮质(OFC)。在这个提案中，我们将使用光遗传学、电生理学和自然气味刺激 自由行为的小鼠，以了解啮齿动物的嗅觉系统如何能够获得感觉信息。 初步研究表明，嗅觉信息在睡眠期间可以到达大脑皮层，而不会衰减，因为 以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 清醒时刺激后伽马振荡增加，但睡眠时不增加。我们假设感官 反应(伽马振荡除外)在睡眠期间大部分保存在嗅觉皮质中，原因是 减少对OB的自上而下的皮质输入，其主要功能是通过增强 局部抑制。我们将在两个目标上检验这一假设。在目标1中，在自然睡眠和清醒状态下，LFP 将从多个嗅觉区域同时记录，并将在 前部PC对光遗传刺激和自然气味刺激的反应 进入鼻腔，以避免在不同大脑状态下改变呼吸的混乱。在目标2中， 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 (即多个肾小球)通过光遗传刺激，单个肾小球将被刺激以使其影响最小化 侧向抑制。此外，记录将在麻醉下进行，以使这一结果与 以往关于这一主题的研究。总之，这些实验将揭示嗅觉信息的差异。 在自然睡眠/清醒状态下的处理，并为这些差异提供了一种机制。

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.