Long-term effects of low prenatal alcohol exposure on GABAergic interneurons of the murine posterior parietal cortex.
Long-term effects of low prenatal alcohol exposure on GABAergic interneurons of the murine posterior parietal cortex.
复制标题
产前低酒精暴露对小鼠后顶叶皮质 GABA 能中间神经元的长期影响。
DOI：
10.1111/acer.15210
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Brigman,JonathanL
中科院分区：
文献类型：
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作者：
Licheri,Valentina;Jacquez,BelkisJ;Castillo,VictoriaK;Sainz,DylanB;Valenzuela,CFernando;Brigman,JonathanL
背景胎儿酒精谱系障碍 (FASD) 的特点是在整个生命周期中发生广泛的身体、认知和行为障碍。产前酒精暴露（PAE）可导致成年后顶叶皮层（PPC）介导的认知控制行为受损。 PPC 在灵长类动物和啮齿动物的反应任务执行中发挥着重要作用，特别是当需要在相似的目标刺激和非目标刺激之间进行选择时。此外，PPC 与其他皮质区域相互连接。尽管有大量文献研究了皮质区介导的 PAE 认知功能损伤的分子机制，但关于 PAE 对 PPC 发育和功能的长期影响知之甚少。在这里，我们使用行为幼稚对照和 PAE 小鼠检查了 GABA 能中间神经元的细胞组织变化及其在 PPC 中的功能。方法我们使用 PAE 的有限进入模型，其中 C57BL/6J 雌性在整个妊娠期间每天暴露于 10% (w/v) 乙醇和 0.066% (w/V) 糖精的溶液中 4 小时。使用高通量荧光显微镜，我们量化了成年 PAE 和对照后代 PPC 中 GABA 能中间神经元的水平。在另一个队列中，我们使用 PPC 5 层锥体神经元的全细胞膜片钳记录记录了自发抑制性突触后电流 (sIPSC)。 结果PAE 导致 PAE 小鼠中表达小白蛋白的 GABA 能中间神经元显着总体减少，无论性别如何。表达生长抑素和钙结合蛋白的 GABA 能中间神经元不受影响。有趣的是，PAE 不会调节 sIPSC 幅度或频率。结论这些结果表明，FASD 中观察到的认知控制受损可能是由于 PPC 中表达小清蛋白的 GABA 能中间神经元显着减少所致。 PAE 动物在这些中间神经元发育减少后可能会表现出 GABA 能功能的代偿性变化。
BackgroundFetal alcohol spectrum disorders (FASDs) are characterized by a wide range of physical, cognitive, and behavioral impairments that occur throughout the lifespan. Prenatal alcohol exposure (PAE) can lead to adult impairments in cognitive control behaviors mediated by the posterior parietal cortex (PPC). The PPC plays a fundamental role in the performance of response tasks in both primates and rodents, specifically when choices between similar target and nontarget stimuli are required. Furthermore, the PPC is reciprocally connected with other cortical areas. Despite the extensive literature investigating the molecular mechanisms underlying PAE impairments in cognitive functions mediated by cortical areas, little is known regarding the long‐term effects of PAE on PPC development and function. Here, we examined changes in the cellular organization of GABAergic interneurons and their function in PPC using behaviorally naïve control and PAE mice.MethodsWe used a limited access model of PAE in which C57BL/6J females were exposed to a solution of 10% (w/v) ethanol and 0.066% (w/V) saccharin for 4 h/day throughout gestation. Using high‐throughput fluorescent microscopy, we quantified the levels of GABAergic interneurons in the PPC of adult PAE and control offspring. In a separate cohort, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole‐cell patch clamp recordings from PPC layer 5 pyramidal neurons.ResultsPAE led to a significant overall reduction of parvalbumin‐expressing GABAergic interneurons in PAE mice regardless of sex. Somatostatin‐ and calretinin‐expressing GABAergic interneurons were not affected. Interestingly, PAE did not modulate sIPSC amplitude or frequency.ConclusionsThese results suggest that impairments in cognitive control observed in FASD may be due to the significant reduction of parvalbumin‐expressing GABAergic interneurons in the PPC. PAE animals may show compensatory changes in GABAergic function following developmental reduction of these interneurons.