Dependence of memory on precisely coordinated oscillations

项目总结 大脑振荡被认为对认知功能至关重要，在所有主要疾病中都会受到干扰 神经和精神障碍，如阿尔茨海默病、癫痫、抑郁症和 精神分裂症。人们对了解神经细胞之间的关系越来越感兴趣。 健康和疾病大脑中的计算和振荡模式，因为振荡模式 可以通过非侵入性和侵入性刺激设备进行靶向治疗。虽然大多数人的大脑 节律由神经元起搏器或局部电路产生，呼吸产生节律 通过外部环路进行大脑活动。鼻腔气流刺激嗅觉感觉神经元产生 嗅球的呼吸相关振荡(RRO)。RRO已经被广泛地证明是 传播到皮质区，包括梨状皮质(PC)、前额叶皮质区、外侧内嗅区 大脑皮层(LEC)和海马区(HC)。在HC中，RRO可以与起搏器并行检测- 产生了theta振荡，这对记忆功能和频率重叠至关重要。它不是 很清楚，这两种类型的振荡在多大程度上只是平行现象或功能上的 协调以支持神经计算。我们假设RRO和theta振荡不会 全局耦合，但跨大脑区域神经元亚群与每个 不同记忆阶段的振荡模式。为了解决这个问题，我们将执行 气味中局部场电位和神经元放电模式的记录和操作 指导性工作记忆任务，其中两种类型的振荡都很突出。在目标1中，我们将 确定RRO、theta振荡和较高频率的振荡是否协调 通过在嗅觉工作记忆任务中记录LFP和/或单个单位来跨越大脑区域 OB、前PC、LEC、腹侧HC、背侧HC和内侧前额叶皮质(MPFC)。这些大脑 之所以包括这些区域，是因为在所有这些区域中都报告了RRO和典型的theta振荡 因为这些大脑区域被认为对工作记忆的表现至关重要。 在目标2中，我们将使用光遗传学来改变RRO和规范theta的频率 振荡，以确定在工作记忆的哪些阶段，它们对任务至关重要 性能。最后，在目标3中，我们将使用气味引导工作的匹配/非匹配版本 记忆任务，以确定最初的感觉代码如何转换为活动模式， 在保留期内保持信息量大。综上所述，我们的目标将揭示神经元 在工作记忆中，活动模式由两种类型的振荡来协调。机械师 理解支持记忆计算的大脑振荡是设计 以及应用脑刺激疗法来改善神经和精神疾病的记忆。

PROJECT SUMMARY Brain oscillations are thought to be critical for cognitive functions and are disrupted in all major neurological and psychiatric disorders, such as Alzheimer’s disease, epilepsy, depression, and schizophrenia. There has been increasing interest in understanding the relation between neural computations and oscillatory patterns in the healthy and diseased brain because oscillation patterns can be targeted for treatment with noninvasive and invasive stimulation devices. While most brain rhythms are generated by either neuronal pacemakers or local circuits, breathing generates rhythmic brain activity by an external loop. Nasal air flow stimulates olfactory sensory neurons which generate respiration-related oscillations (RROs) in the olfactory bulb (OB). RROs have been shown to widely propagate to cortical areas, including piriform cortex (PC), prefrontal cortical areas, lateral entorhinal cortex (lEC), and hippocampus (HC). In HC, RROs can be detected in parallel with pacemaker- generated theta oscillations, which are critical for memory function and overlap in frequency. It is not clear to what extent the two types of oscillations are merely parallel phenomena or functionally coordinated to support neural computations. We hypothesize that RROs and theta oscillations do not globally couple, but that subpopulations of neurons across brain regions are synchronized with each oscillation pattern across different memory phases. To address this question, we will perform recordings and manipulations of local field potentials (LFPs) and neuronal firing patterns in odor- guided working memory tasks, where both types of oscillations are prominent. In Aim 1, we will determine whether RROs, theta oscillations, and oscillations at higher frequencies are coordinated across brain regions in an olfactory working memory task by recording LFPs and/or single-units in the OB, anterior PC, lEC, ventral HC, dorsal HC, and medial prefrontal cortex (mPFC). These brain regions are included because RROs and canonical theta oscillations have been reported in all of these regions and because these brain regions are thought to be critical for working memory performance. In Aim 2, we will then use optogenetics to change the frequency of RROs and canonical theta oscillations to determine during which phases of working memory they are critical for task performance. Finally, in Aim 3, we will use a match/non-match version of the odor-guided working memory task to determine how the initial sensory code is transformed into activity patterns that remain informative over the retention interval. Taken together, our aims will reveal how neuronal activity patterns are coordinated by two types of oscillations during working memory. A mechanistic understanding of brain oscillations that support memory computations is foundational for devising and applying brain stimulation therapies to improve memory in neurological and psychiatric diseases.