Prenatal alcohol exposure reduces the size of the forelimb representation in motor cortex in rat: an intracortical microstimulation (ICMS) mapping study.
Prenatal alcohol exposure reduces the size of the forelimb representation in motor cortex in rat: an intracortical microstimulation (ICMS) mapping study.
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产前酒精暴露会减少大鼠运动皮层前肢的大小：一项皮质内微刺激（ICMS）绘图研究。
DOI：
10.1016/j.alcohol.2009.10.014
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Waters,RobertS
中科院分区：
文献类型：
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作者：
Xie,Ni;Yang,Qiuhong;Chappell,TysonD;Li,Cheng-Xiang;Waters,RobertS
患有胎儿酒精谱系障碍（FASD）的儿童通常表现出感觉运动功能障碍，包括运动协调和精细运动控制方面的缺陷。虽然这些运动异常的根本原因尚不清楚，但它们可能涉及感觉和运动系统之间的相互作用。啮齿类动物模型已被用来研究产前酒精暴露（PAE）的影响，熟练的达到和体感桶场皮层的发展和组织。为此，PAE延迟了躯体感觉皮层的发育，减小了躯体感觉桶场皮层中的触须和前肢表征的大小，并延迟了学习熟练达到任务的获取时间。然而，PAE是否也影响运动皮层（MI）仍有待确定。在本研究中，我们研究了PAE对大鼠MI中前肢表示的大小，激活阈值以及感觉运动皮层中运动和感觉皮层前肢地图之间的重叠的影响。在妊娠第1天（GD1），将妊娠Sprague-Dawley大鼠分配至酒精（Alc）、配对喂养（PF）和饲料喂养（CF）组。从GD1至GD20，Alc组大鼠（n = 4）每天长期插管，给予过量酒精（6g/kg体重），导致GD10（平均值= 191.5 ± 41.9mg/dL）和GD17（平均值= 247.0 ± 72.4mg/dL）测量的平均血液酒精水平。PF组（n = 2）和CF组（n = 3）为对照组。从给药组内每只母鼠的多只雄性后代中获得PAE对各种依赖性指标的影响，并比较了酒精给药组和对照组（Ct：CF和PF）母鼠的窝平均值。在约8周龄时，用氯胺酮/甲苯噻嗪麻醉大鼠，并在感觉运动皮质上打开颅骨。然后将钨微电极插入V层深处，并使用皮质内微刺激来传递脉冲串以引起肌肉收缩和/或运动;最大刺激≤ 100 μ A。当观察到运动反应时，测量运动阈值，并将运动感受野投射到皮质表面，作为该位置的代表点。通过在相邻部位系统地刺激直到电流阈值达到最大值和/或不再诱发运动反应来生成用于前肢表示的运动图。这项研究的主要结果如下：（1）PAE显著减小了Alc子代前肢表征的面积（6.01mm~2，平均标准误= ± 0.278）（8.03mm~2 ± 0.586）;（2）PAE组间平均动作激活阈值无明显降低;（3）PAE显著降低了感觉和运动皮质中前肢代表之间的重叠百分比（Alc = 31.1%，Ct = 55.4%），并且（4）未观察到处理组之间的平均体重、半球重量或动物年龄的显著差异。这些研究结果表明，PAE的影响不仅限于体感桶场皮层，而且还涉及MI，并可能是在FASD儿童中观察到的运动控制和感觉运动整合缺陷的基础。
Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems. Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on the development and organization of somatosensory barrel field cortex. To this end, PAE delayed the development of somatosensory cortex, reduced the size of whisker and forelimb representations in somatosensory barrel field cortex, and delayed acquisition time to learn a skilled reaching task. However, whether PAE also affects the motor cortex (MI) remains to be determined. In the present study, we investigated the effect of PAE on the size of the forelimb representation in rat MI, thresholds for activation, and the overlap between motor and sensory cortical forelimb maps in sensorimotor cortex. Pregnant Sprague–Dawley rats were assigned to alcohol (Alc), pair-fed (PF), and chow-fed (CF) groups on gestation day 1 (GD1). Rats in the Alc group (n=4) were chronically intubated daily with binge doses of alcohol (6g/kg body weight) from GD1 to GD20 that resulted in averaged blood alcohol levels measured on GD10 (mean=191.5±41.9mg/dL) and on GD17 (mean=247.0±72.4mg/dL). PF (n=2) and CF (n=3) groups of pregnant rats served as controls. The effect of PAE on the various dependent measures was obtained from multiple male offspring from each dam within treatment groups, and litter means were compared between the groups from alcohol-treated and control (Ct: CF and PF) dams. At approximately 8 weeks of age, rats were anesthetized with ketamine/xylazine and the skull opened over sensorimotor cortex. A tungsten microelectrode was then inserted into the depths of layer V and intracortical microstimulation was used to deliver trains of pulses to evoke muscle contractions and/or movements; maximum stimulating ≤100μA. When a motor response was observed, the threshold for movement was measured and the motor receptive field projected to the cortical surface to serve as representative point for that location. A motor map for the forelimb representation was generated by systematically stimulating at adjacent sites until current thresholds reached the maximum and/or motor responses were no longer evoked. The major findings in this study were as follows: (1) PAE significantly reduced the area of the forelimb representation in the Alc offspring (6.01mm2, standard error of the mean=±0.278) compared with the Ct offspring (8.03mm2±0.586), (2) PAE did not significantly reduce the averaged threshold for activation of movements between groups, (3) PAE significantly reduced the percent overlap (Alc=31.1%, Ct=55.4%) between the forelimb representation in sensory and motor cortices, and (4) no significant differences were observed in averaged body weight, hemisphere weight, or age of animal between treatment groups. These findings suggest that the effects of PAE are not restricted to somatosensory barrel field cortex but also involve the MI and may underlie deficits in motor control and sensorimotor integration observed among children with FASD.