Subcortical influence on the respiratory coordination of cortical neurodynamics related 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: 10652899
• 负责人: JAMES M MCNALLY
• 金额: $ 19.62万
• 依托单位: BOSTON VA RESEARCH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10652899
• 关键词: Animals; Attention; Behavior; Brain; Brain region; Cell Nucleus; Characteristics; 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; 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; neurological pathology; neuropsychiatric disorder; neuropsychiatry; novel; novel diagnostics; novel therapeutic intervention; olfactory bulb; optogenetics; relating to nervous system; respiratory; response; sustained attention; translational therapeutics; vigilance; way finding

Slow cortical oscillations, such as theta (5-9Hz) band activity, may provide 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. The role of theta/GBO coupling (TG coupling) in cognitive processing is well established. However, more recent studies have observed that nasal respiration can also temporally coordinate dynamic neural activity in the brain, reflected as respiratory-entrained oscillations (REO), which 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 attention-related performance. Aim 1: RG coupling in the frontoparietal attentional network correlates with performance in an attention-demanding operant task. We will measure respiration and REO in local field potentials in select brain regions to evaluate RG coupling during an operant signal detection task used to measure sustained 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 BF parvalbumin neurons (BF-PV) will impair/improve attention-related performance in the rPVT. Our preliminary findings show that closed-loop gamma frequency stimulation (CLS) of BF-PV in relation to respiratory inhalation, but not exhalation, promotes RG coupling. Therefore, we will utilize this CLS paradigm to determine how modulation of RG coupling impacts attention-related performance. Across a range of select neuropsychiatric illnesses, the pathological processes behind cognitive deficits involve abnormal neural temporal dynamics. Thus, these studies will help to inform the development of translational therapies to restore/enhance cognitive function.

缓慢的皮层振荡，如θ（5- 9 Hz）带活动，可以提供活动的连贯性超过大 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。theta/GBO耦合（TG耦合）在认知加工中的作用是很好的 确立了习然而，最近的研究发现，鼻呼吸也可以暂时 协调大脑中的动态神经活动，反映为自发振荡（REO）， 在选择行为期间表现出与GBO的高相位-幅度耦合（RG耦合）。目前尚不清楚 RG耦合是否在认知中起作用我们的总体假设假定，RG耦合的强度， 与注意力相关的额顶叶网络（前边缘和后顶叶皮质）将与 注意力相关的表现。 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。我们将测量呼吸和REO在局部场电位在选择 在用于测量持续性的操作性信号检测任务期间， 注意，啮齿动物的心理警觉任务（rPVT）。在rPVT中，小鼠保持对刺激的注意力 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性反应， 获得食物奖励。在正确的试验之前，我们预测RG耦合在额顶叶中将是强有力的。 注意力网络，并且更快的反应时间将与鲁棒的RG耦合相关。相比之下， 遗漏试验（注意失败），我们预测RG耦合将减少。 目的2：通过BF的光遗传学操作减弱/促进RG偶联 小清蛋白神经元（BF-PV）将损害/改善rPVT中的注意力相关表现。我们 初步研究结果表明，BF-PV的闭环伽马频率刺激（CLS）与 呼吸吸气而不是呼气促进RG偶联。因此，我们将利用这个CLS范例， 确定RG耦合的调制如何影响与注意力相关的表现。 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，这些研究将有助于了解 转化疗法，以恢复/增强认知功能。