Delta oscillations are a robust biomarker of dopamine depletion severity and motor dysfunction in awake mice.
Delta oscillations are a robust biomarker of dopamine depletion severity and motor dysfunction in awake mice.
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Delta振荡是清醒小鼠多巴胺耗竭严重程度和运动功能障碍的强有力的生物标志物。
DOI：
10.1152/jn.00158.2020
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发表时间：
2020
影响因子：
2.5
通讯作者：
Gittis,ArynH
中科院分区：
文献类型：
--
作者：
Whalen,TimothyC;Willard,AmandaM;Rubin,JonathanE;Gittis,ArynH
δ振荡（0.5-4 Hz）是帕金森病（PD）患者基底神经节病理生理学的一个稳健特征，与震颤有关，但尚未研究其与其他帕金森症状的关系。虽然在PD小鼠模型中观察到δ振荡，但仅在麻醉动物中进行了研究，这表明振荡可能是麻醉伪影，并限制了将其与运动症状联系起来的能力。在这里，我们建立了一种新的方法来检测嵌入在噪声中的尖峰振荡，以提供在清醒的多巴胺耗尽的小鼠中的δ振荡的第一个研究。我们发现，在黑质网状部（SNr）的神经元中，大约有一半表现出多巴胺耗竭的δ振荡，这些振荡是多巴胺丢失和运动不能的一个强有力的指标，优于放电率，不规则性，突发性和同步性的变化等措施。这些振荡通常在运动期间被减弱，但不被消融。我们进一步证实，这些振荡是由D2受体激活的丧失引起的，并不起源于运动皮层，与以前在麻醉动物中的发现相反。相反，SNr振荡先于M1振荡，滞后100- 300 ms，这些神经元与M1振荡的关系可以作为SNr分为两个亚群的新分类的基础。这些结果深入了解了多巴胺损失如何导致运动功能障碍，并建议重新评估Delta振荡作为PD运动不能症状的标志。新&值得注意这项工作介绍了一种在神经噪音中检测尖峰振荡的新方法。使用这种方法，我们表明，在基底神经节的δ振荡是清醒的，多巴胺耗尽的小鼠的一个定义功能，并与多巴胺的损失和帕金森氏症的运动症状密切相关。这些振荡是由D2受体激活的丧失引起的，不需要运动皮层。人类患者的类似振荡可能是帕金森病（PD）治疗的一个未被充分认识的标志物和目标。
Delta oscillations (0.5–4 Hz) are a robust feature of basal ganglia pathophysiology in patients with Parkinson’s disease (PD) in relationship to tremor, but their relationship to other parkinsonian symptoms has not been investigated. While delta oscillations have been observed in mouse models of PD, they have only been investigated in anesthetized animals, suggesting that the oscillations may be an anesthesia artifact and limiting the ability to relate them to motor symptoms. Here, we establish a novel approach to detect spike oscillations embedded in noise to provide the first study of delta oscillations in awake, dopamine-depleted mice. We find that approximately half of neurons in the substantia nigra pars reticulata (SNr) exhibit delta oscillations in dopamine depletion and that these oscillations are a strong indicator of dopamine loss and akinesia, outperforming measures such as changes in firing rate, irregularity, bursting, and synchrony. These oscillations are typically weakened, but not ablated, during movement. We further establish that these oscillations are caused by the loss of D2-receptor activation and do not originate from motor cortex, contrary to previous findings in anesthetized animals. Instead, SNr oscillations precede those in M1 at a 100- to 300-ms lag, and these neurons’ relationship to M1 oscillations can be used as the basis for a novel classification of SNr into two subpopulations. These results give insight into how dopamine loss leads to motor dysfunction and suggest a reappraisal of delta oscillations as a marker of akinetic symptoms in PD.NEW & NOTEWORTHYThis work introduces a novel method to detect spike oscillations amidst neural noise. Using this method, we demonstrate that delta oscillations in the basal ganglia are a defining feature of awake, dopamine-depleted mice and are strongly correlated with dopamine loss and parkinsonian motor symptoms. These oscillations arise from a loss of D2-receptor activation and do not require motor cortex. Similar oscillations in human patients may be an underappreciated marker and target for Parkinson’s disease (PD) treatment.