Jandó G, Carpi D, Kandel A, Urioste R, Horvath Z, Pierre E, Vadi D, Vadasz C, Buzsáki G
Center for Molecular and Behavioural Neuroscience, Rutgers, State University of New Jersey, Newark 07102, USA.
Neuroscience. 1995 Jan;64(2):301-17. doi: 10.1016/0306-4522(94)00329-4.
Spontaneously occurring spike-and-wave patterns were examined in seven to eight-month-old rats of the inbred Fischer 344 and Brown Norway strains and their F1 and F2 hybrids. Neocortical activity and movement were monitored for 12 night h. Spike-and-wave episodes were identified by a three-layer back-propagation neural network. The incidence, average duration and total duration of spike-and-wave episodes were significantly higher in F1 males and F2 hybrids than in the parental strains. Male rats of the Brown Norway strain had significantly more and longer episodes than females, whereas no sex differences were present in Fischer rats. The average intraepisodic frequency of spike-and-wave patterns was significantly lower in Fischer rats than in the other groups and significantly higher in males than females. Tremor (myoclonic movements) associated with spike-and-wave episodes was absent or of very small amplitude in Fischer rats but frequent and of large amplitude in Brown Norway rats and their F1 and F2 descendants. Most of the interstrain differences were limited to male rats. Spike-and-wave episodes recurred at predictable short-term (10-30 s) and long-term (15-30 min) periods. The long-term oscillation corresponded to a similar fluctuation of motor activity. The maximum probability of spike-and-wave patterns occurred at a relatively narrow range of delta power (0-3.1 Hz) of the background EEG activity. Systemic administration of the adrenergic alpha-2 agonist, clonidine, increased the incidence of spike-and-wave episodes several-fold. The total duration of spike-and-wave episodes in the clonidine sessions (15 min) and night sessions (12 h test) correlated significantly. We suggest that several genes interact with maturational, environmental and endocrine factors, resulting in sex differences, and produce the variety of EEG and behavioral findings encountered. In addition, we submit that the clonidine test may be useful in genetic investigations of human absence epilepsies. The findings of this work demonstrate that genetic manipulation of rodents is a promising method for producing analogous models for the various forms of human absence epilepsies.
在近交系Fischer 344和Brown Norway品系及其F1和F2杂种的7至8月龄大鼠中，研究了自发出现的棘波-慢波模式。对新皮质活动和运动进行了12个夜间小时的监测。通过三层反向传播神经网络识别棘波-慢波发作。F1雄性大鼠和F2杂种的棘波-慢波发作的发生率、平均持续时间和总持续时间显著高于亲本品系。Brown Norway品系的雄性大鼠发作次数明显更多、持续时间更长，而Fischer大鼠不存在性别差异。Fischer大鼠棘波-慢波模式的平均发作期频率显著低于其他组，且雄性高于雌性。与棘波-慢波发作相关的震颤（肌阵挛运动）在Fischer大鼠中不存在或幅度非常小，但在Brown Norway大鼠及其F1和F2后代中频繁且幅度大。大多数品系间差异仅限于雄性大鼠。棘波-慢波发作在可预测的短期（10 - 30秒）和长期（15 - 30分钟）周期内复发。长期振荡对应于运动活动的类似波动。棘波-慢波模式的最大概率出现在背景脑电图活动的相对较窄的δ功率范围（0 - 3.1赫兹）内。全身性给予肾上腺素能α-2激动剂可乐定，使棘波-慢波发作的发生率增加了几倍。可乐定给药期间（15分钟）和夜间时段（12小时测试）的棘波-慢波发作总持续时间显著相关。我们认为，几个基因与成熟、环境和内分泌因素相互作用，导致性别差异，并产生所观察到的各种脑电图和行为结果。此外，我们提出可乐定试验可能有助于人类失神癫痫的基因研究。这项工作的结果表明，对啮齿动物进行基因操作是产生各种形式人类失神癫痫类似模型的一种有前途的方法。
