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.

缓慢的皮层振荡，如θ波活动（5- 9 Hz），可能是至关重要的活动的连贯性， 大的距离，提供了一种机制，跨区域通信参与神经处理。快 伽马波段振荡（GBO; 30-200 Hz）被认为在更高层次的认知中起主要作用。 处理包括注意力。虽然Theta/GBO耦合在认知加工的某些方面的作用 一直是一个非常感兴趣的话题，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。这些振荡也表现出高相位， 在选择行为期间，振幅耦合到GBO（RG耦合）。目前尚不清楚RG耦合是否具有 a role作用in cognition认知.我们的总体假设假定，RG耦合的强度在注意- 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。 目的1：额顶叶注意网络中的RG耦合与一个人的表现相关。 需要注意力的操作性任务。我们将在当地测量呼吸和蒸发夹带振荡， 选择脑区域的场电位，以评估操作性信号检测任务期间的RG耦合， 测量警觉注意力，啮齿动物心理警觉任务（rPVT）。在rPVT中，小鼠保持注意力 一个刺激位置，并响应检测到一个简短的和不可预测的线索与短潜伏期的操作 获得食物奖励。在正确的试验之前，我们预测RG偶联将在 额顶叶注意力网络，以及更快的反应时间将与强大的RG耦合。与此相反， 在遗漏试验（注意力缺失）之前，我们预测RG耦合将减少。 目的2：通过基底膜的光遗传学操作减弱/促进RG偶联。 前脑小清蛋白神经元将损害/改善rPVT中的表现。我们的初步研究结果 显示了基底前脑小清蛋白神经元闭环γ频率刺激与 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 范例来确定RG耦合的调制如何影响rPVT中的性能。 在一系列神经精神疾病中，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告知 开发转化疗法以恢复/增强认知功能。