超声发声 - 大鼠中与癫痫相关的新表现。
Ultrasonic vocalizations - Novel seizure-related manifestation in rats.
机构信息
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
出版信息
Epilepsy Res. 2022 Jul;183:106927. doi: 10.1016/j.eplepsyres.2022.106927. Epub 2022 Apr 22.
OBJECTIVE
Seizures of frontal or temporal lobe origin can associate with vocalizations in humans. Our objective was to assess whether rats emit specific seizure-related patterns of ultrasonic vocalizations (USVs) during seizures and epileptiform activity.
METHODS
Adult male Sprague-Dawley rats were treated with a single administration of pentylenetetrazol (PTZ, 50 mg/kg, i.p.) and monitored with simultaneous USV and video-electroencephalogram recordings for up to 15 min. USVs were detected using a deep learning algorithm (DeepSqueak-Screener) and manually annotated into the 15 previously described subcategories. The number, frequency, duration, sonographic structure, and temporal relationship of the USVs to seizures and epileptiform activity were assessed.
RESULTS
A total of 2147 USVs were recorded in 12 rats that expressed a total of 22 PTZ-induced seizures. Of the USVs, 77% were in the 50-kHz range (i.e., appetitive state) and 23% in the 22-kHz ( i.e., aversive state) range. More than a third (37%) of the USVs could be classified into 1 of the 15 call subcategories; the remaining 63% belonged to a novel "multiform" USV category with a complex sonographic structure. Of the 2147 USVs, 23% occurred during the PTZ-induced seizures and 77% during other types of PTZ-induced epileptiform activity. Almost all (19/22) of seizures were associated with USVs. In each rat, the first seizure was always associated with a USV. The shorter the latency to the first USV, the shorter the latency to the onset of the first electrographic seizure (r = 0.995, p < 0.001). The greater the number of USVs, the greater the number of seizures (r = 0.916, p < 0.001) and the longer the total seizure duration in a given rat (r = 0.750, p < 0.05).
SIGNIFICANCE
Like in humans, vocalizations are a seizure-related behavioral feature in rats and recording USVs provides a novel noninvasive tool for detecting experimental seizures. Further studies are needed to explore USV occurrence during spontaneous seizures and their potential for screening novel anti-seizure drugs.
目的
起源于额叶或颞叶的癫痫发作可伴有人类的发声。我们的目的是评估大鼠在癫痫发作和癫痫样活动期间是否会发出特定的与癫痫发作相关的超声发声（USV）模式。
方法
成年雄性 Sprague-Dawley 大鼠单次给予戊四氮（PTZ，50mg/kg，ip）治疗，并通过同时进行 USV 和视频-脑电图记录进行监测，最长达 15 分钟。使用深度学习算法（DeepSqueak-Screener）检测 USV，并手动注释为之前描述的 15 个子类别中的 1 个。评估 USV 的数量、频率、持续时间、超声结构以及与癫痫发作和癫痫样活动的时间关系。
结果
在 12 只表达总共 22 次 PTZ 诱导性癫痫发作的大鼠中，共记录到 2147 个 USV。其中，77%的 USV 处于 50-kHz 范围（即，渴望状态），23%处于 22-kHz 范围（即，厌恶状态）。超过三分之一（37%）的 USV 可归类为 15 个叫声亚类中的 1 个；其余 63%属于具有复杂超声结构的新型“多形式”USV 类别。在 2147 个 USV 中，有 23%发生在 PTZ 诱导的癫痫发作期间，77%发生在其他类型的 PTZ 诱导的癫痫样活动期间。几乎所有（19/22）的癫痫发作都与 USV 相关。在每只大鼠中，第一次癫痫发作总是与 USV 相关。首次 USV 的潜伏期越短，首次脑电图癫痫发作的潜伏期越短（r=0.995，p<0.001）。USV 的数量越多，癫痫发作的数量就越多（r=0.916，p<0.001），特定大鼠的总癫痫发作持续时间就越长（r=0.750，p<0.05）。
意义
与人类一样，发声是大鼠癫痫发作相关的行为特征，记录 USV 为检测实验性癫痫发作提供了一种新的非侵入性工具。需要进一步的研究来探索自发性癫痫发作期间 USV 的发生及其作为新型抗癫痫药物筛选的潜力。
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