Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
Island Medical Program, Department of Cellular and Physiological Sciences, University of British Columbia, Victoria, BC, Canada.
Alcohol Clin Exp Res. 2019 Oct;43(10):2153-2166. doi: 10.1111/acer.14170. Epub 2019 Aug 26.
The hippocampus is particularly vulnerable to the teratogenic effects of prenatal ethanol exposure (PNEE), and hippocampal structural and functional deficits are thought to contribute to the learning and memory deficits that are a hallmark feature of fetal alcohol spectrum disorders.
Sprague Dawley dams were exposed to a liquid diet that contained EtOH (35.5% EtOH-derived calories) throughout gestation, and then, PNEE juvenile (P21-28) male and female offspring were used for in vitro electrophysiological recordings. We examined long-term potentiation (LTP), long-term depression (LTD), and depotentiation in the medial perforant path input to the dentate gyrus (DG) to determine the impact of PNEE on the dynamic range of bidirectional synaptic plasticity in both sexes.
PNEE reduced the responsiveness of the DGs of male but not in female offspring, and this effect was no longer apparent when GABAergic signaling was inhibited. There was also a sex-specific LTD impairment in males, but increasing the duration of the conditioning stimulus could overcome this deficit. The magnitude of LTP was also reduced, but in both sexes following PNEE. This appears to be an increase in the threshold for induction, not in capacity, as the level of LTP induced in PNEE animals was increased to control levels when additional conditioning stimuli were administered.
These data are the first to describe, in a single study, the impact of PNEE on the dynamic range of bidirectional synaptic plasticity in the juvenile DG in both males and in females. The data suggest that PNEE increases the threshold for LTP in the DG in both sexes, but produces a sex-specific increase in the threshold for LTD in males These alterations reduce the dynamic range for synaptic plasticity in both sexes.
海马体特别容易受到产前乙醇暴露（PNEE）的致畸作用的影响，并且海马体的结构和功能缺陷被认为是导致学习和记忆缺陷的原因，这些缺陷是胎儿酒精谱系障碍的一个显著特征。
Sprague Dawley 母鼠在整个孕期内接受含有乙醇（35.5%的乙醇衍生卡路里）的液体饮食，然后对 PNEE 幼鼠（P21-28）雄性和雌性后代进行体外电生理记录。我们检查了内侧穿通路径到齿状回（DG）的长时程增强（LTP）、长时程抑制（LTD）和再去极化，以确定 PNEE 对两性双向突触可塑性的动态范围的影响。
PNEE 降低了雄性后代 DG 的反应性，但对雌性后代没有影响，当抑制 GABA 能信号时，这种影响就不再明显。雄性还存在特定的 LTD 损伤，但增加条件刺激的持续时间可以克服这种缺陷。LTP 的幅度也降低了，但在 PNEE 后在两性中都是如此。这似乎是诱导阈值的增加，而不是容量的增加，因为在给予额外的条件刺激时，PNEE 动物诱导的 LTP 幅度增加到对照水平。
这些数据首次描述了在单一研究中，PNEE 对雄性和雌性幼鼠 DG 双向突触可塑性动态范围的影响。数据表明，PNEE 增加了 DG 中 LTP 的阈值，而在雄性中则产生了 LTD 阈值的性别特异性增加。这些改变降低了两性的突触可塑性动态范围。
