Subcortical influence on the respiratory coordination of cortical neurodynamicsrelated to cognition

缓慢的皮层振荡，例如theta频段的活动(5-9赫兹)，可能是活动的连贯性的关键 大距离，为参与神经处理的区域间通信提供了一种机制。更快 伽马频段振荡(GBO；30-200赫兹)被认为在更高水平的认知中起着重要作用 包括注意力在内的处理。而Theta/GBO耦合在认知加工的某些方面所起的作用 一直是人们非常感兴趣的话题，最近的研究结果表明，鼻腔呼吸也可以暂时 协调大脑中的动态神经活动。这些呼吸携带的振荡也表现出高相位- 选择行为期间的幅度耦合到GBO(RG耦合)。目前还不清楚RG联轴器是否有 认知中的一个角色。我们的主要假设是RG在注意力上的耦合强度- 相关的额顶网络(前顶叶和后顶叶皮质)将与警惕的注意力相关- 依赖于性能。 目的1：额顶叶注意网络中的RG偶联与学习成绩相关 需要集中注意力的操作性任务。我们将在当地测量呼吸和呼吸携带的振荡 用于在操作信号检测任务期间评估RG耦合的选定脑区的场电位 测量警觉注意、啮齿动物精神运动警戒任务(RPVT)。在rPVT中，小鼠保持注意力 到刺激位置，并用短潜伏期操作符响应于检测到短暂且不可预测的提示 回应收到食物奖励。在正确的试验之前，我们预测RG耦合将在 额顶叶注意网络，快速反应时间将与强健的RG耦合相关。相比之下， 在遗漏试验(注意力失败)之前，我们预测RG的耦合将会减弱。 目的2：通过基底膜的光遗传操作减弱/促进RG偶联 前脑小白蛋白神经元将损害/改善rPVT的表现。我们的初步调查结果 显示闭环伽马频率刺激与基底前脑小白蛋白神经元的关系 呼吸吸气，而不是呼气，促进RG偶联。因此，我们将利用这种刺激 用于确定RG耦合的调制如何影响rPVT中的性能的范例。 在一系列精选的神经精神疾病中，认知缺陷背后的病理过程 涉及异常的神经时间动力学。因此，这些基础研究将有助于向 发展翻译疗法以恢复/增强认知功能。

Slow cortical oscillations, such as theta band activity (5-9Hz), may be critical for coherence of activity over large distances, providing a mechanism for interregional communication involved in neural processing. Faster gamma band oscillations (GBO; 30-200 Hz) are thought to play a major role in higher-level cognitive processing including attention. While the role of Theta/GBO coupling in select aspects of cognitive processing has been a topic of intense interest, recent findings suggest that nasal respiration can also temporally coordinate dynamic neural activity in the brain. These respiratory-entrained oscillations also exhibit high phase- amplitude coupling to GBO (RG coupling) during select behaviors. Presently it is unknown if RG coupling has a role in cognition. Our overarching hypothesis posits that the strength of RG coupling in the attention- related frontoparietal network (prelimbic and posterior parietal cortices) will correlate with vigilant attention- dependent performance. Aim 1: RG coupling in the frontoparietal attentional network correlates with performance in an attention-demanding operant task. We will measure respiration and respiratory-entrained oscillations in local field potentials in select brain regions to evaluate RG coupling during an operant signal detection task used to measure vigilant attention, the rodent psychomotor vigilance task (rPVT). In the rPVT, mice maintain attention to a stimulus location, and respond to detection of a brief and unpredictable cue with a short-latency operant response to receive food reward. Prior to correct trials, we predict that RG coupling will be strong in the frontoparietal attention network, and that fast reaction times will correlate with robust RG coupling. In contrast, prior to omission trials (attention failures), we predict that RG coupling will be diminished. Aim 2: Attenuation/promotion of RG coupling by means of optogenetic manipulation of basal forebrain parvalbumin neurons will impair/improve performance in the rPVT. Our preliminary findings show that closed-loop gamma frequency stimulation of basal forebrain parvalbumin neurons in relation to respiratory inhalation, but not exhalation, promotes RG coupling. Therefore, we will utilize this stimulation paradigm to determine how modulation of RG coupling impacts performance in the rPVT. Across a range of select neuropsychiatric illnesses, the pathological processes behind cognitive deficits involve abnormal neural temporal dynamics. Thus, these basic research studies will help to inform the development of translational therapies to restore/enhance cognitive function.