Subcortical influence on the respiratory coordination of cortical neurodynamicsrelated to cognition

皮质下对认知相关皮质神经动力学呼吸协调的影响

• 批准号: 10302446
• 负责人: JAMES M MCNALLY
• 金额: $ 16.67万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302446
• 关键词: Animals; Attention; Basic Science; Behavior; Brain; Brain region; Cell Nucleus; Cognition; Cognitive; Cognitive deficits; Communication; Conscious; Coupling; Cues; Data; Detection; Development; Disease; Exhalation; Exhibits; Failure; Food; Frequencies; Hippocampus (Brain); Impaired cognition; Impairment; In Vitro; Inhalation; Investigation; Light; Location; Measures; Mechanical Stimulation; Memory; Mental disorders; Mus; Nasal Epithelium; Neurons; Nose; Parietal Lobe; Parvalbumins; Pathologic Processes; Perception; Performance; Phase; Physiology; Play; Protocols documentation; Reaction Time; Reporting; Research; Respiration; Rewards; Rodent; Role; Sensory; Signal Transduction; Stimulus; Task Performances; Testing; Tort; Training; Validation; Variant; Visual Cortex; Visual attention; Work; attenuation; basal forebrain; cognitive enhancement; cognitive function; disabling symptom; improved; interest; neurological pathology; neuropsychiatric disorder; neuropsychiatry; novel; novel diagnostics; novel therapeutic intervention; olfactory bulb; optogenetics; relating to nervous system; research study; respiratory; response; vigilance; way finding

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.

缓慢的皮质振荡，例如 θ 带活动 (5-9Hz)，可能对于活动的连贯性至关重要 远距离，为涉及神经处理的区域间通信提供了机制。快点 伽马带振荡（GBO；30-200 Hz）被认为在高级认知中发挥着重要作用 处理包括注意力。而 Theta/GBO 耦合在认知处理的某些方面的作用 一直是人们强烈关注的话题，最近的研究结果表明鼻呼吸也可以暂时 协调大脑中的动态神经活动。这些呼吸引起的振荡也表现出高相位 选择行为期间与 GBO 的幅度耦合（RG 耦合）。目前尚不清楚 RG 耦合是否具有 在认知中发挥作用。我们的总体假设认为 RG 耦合在注意力中的强度 相关的额顶叶网络（前边缘和后顶叶皮质）将与警惕的注意力相关 依赖性能。 目标 1：额顶叶注意力网络中的 RG 耦合与行为表现相关 需要注意力的操作任务。我们将测量局部的呼吸和呼吸引起的振荡 选定大脑区域的场电位，以评估操作信号检测任务期间的 RG 耦合 测量警惕注意力，啮齿动物精神运动警惕任务（rPVT）。在 rPVT 中，小鼠保持注意力 到刺激位置，并用短延迟操作响应检测到短暂且不可预测的提示 响应以获得食物奖励。在正确的试验之前，我们预测 RG 耦合在 额顶注意力网络，快速反应时间将与强大的 RG 耦合相关。相比之下， 在遗漏试验（注意失败）之前，我们预测 RG 耦合将会减弱。 目标 2：通过基础光遗传学操作减弱/促进 RG 耦合 前脑小清蛋白神经元会损害/改善 rPVT 的表现。我们的初步调查结果 显示基底前脑小白蛋白神经元的闭环伽马频率刺激与 呼吸促进 RG 耦合，但呼气不促进。因此，我们将利用这种刺激 确定 RG 耦合调制如何影响 rPVT 性能的范例。 在一系列特定的神经精神疾病中，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为 开发转化疗法以恢复/增强认知功能。