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

基本信息

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
项目类别：
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

项目摘要

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.

缓慢的皮质振荡，例如 theta (5-9Hz) 频带活动，可以提供大范围内活动的一致性。距离，为神经处理中涉及的区域间交流提供了一种机制。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。 theta/GBO 耦合（TG 耦合）在认知处理中的作用很好已确立的。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，反映为呼吸引起的振荡（REO），在选择行为期间表现出与 GBO（RG 耦合）的高相位幅度耦合。目前尚不清楚 RG 耦合是否在认知中发挥作用。我们的总体假设认为 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）将与与注意力相关的表现。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。我们将测量选定区域的局部场电位中的呼吸作用和 REO 在用于测量持续的操作信号检测任务期间评估 RG 耦合的大脑区域注意力，啮齿动物精神运动警惕任务（rPVT）。在 rPVT 中，小鼠保持对刺激的注意力位置，并通过短延迟操作响应来响应检测到的简短且不可预测的提示获得食物奖励。在正确的试验之前，我们预测 RG 耦合在额顶叶会很强注意力网络，快速反应时间将与强大的 RG 耦合相关。相比之下，之前遗漏试验（注意失败），我们预测 RG 耦合将会减弱。目标 2：通过 BF 的光遗传学操作来减弱/促进 RG 耦合小清蛋白神经元 (BF-PV) 将损害/改善 rPVT 中与注意力相关的表现。我们的初步结果表明，BF-PV 的闭环伽马频率刺激 (CLS) 与呼吸促进 RG 耦合，但呼气不促进。因此，我们将利用这个 CLS 范式来确定 RG 耦合的调制如何影响注意力相关的表现。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，这些研究将有助于为以下领域的发展提供信息：恢复/增强认知功能的转化疗法。