From the, Indiana University-Purdue University, (MDM, CCL), Indianapolis, Indiana.
University of New Mexico Health Sciences Center, (DNL), Albuquerque, New Mexico.
Alcohol Clin Exp Res. 2020 Nov;44(11):2225-2238. doi: 10.1111/acer.14463. Epub 2020 Oct 16.
BACKGROUND: The medial prefrontal cortex (mPFC) is a brain region involved in the evaluation and selection of motivationally relevant outcomes. Neural activity in mPFC is altered following acute ethanol (EtOH) use and, in rodent models, doses as low as 0.75 g/kg yield cognitive deficits. Deficits in decision making following acute EtOH are thought to be mediated, at least in part, by decreases in mPFC firing rates (FRs). However, the data leading to this conclusion have been generated exclusively in anesthetized rodents. The present study characterizes the effects of acute EtOH injections on mPFC neural activity in awake-behaving rodents. METHODS: Awake-behaving and anesthetized in vivo electrophysiological recordings were performed. We utilized 3 groups: the first received 2 saline injections, the second received a saline injection followed by 1.0 g/kg EtOH, and the last received saline followed by 2 g/kg EtOH. One week later, an anesthetized recording occurred where a saline injection was followed by an injection of 1.0 g/kg EtOH. RESULTS: The anesthetized condition showed robust decreases in neural activity and differences in up-down states (UDS) dynamics. In the awake-behaving condition, FRs were grouped according to behavioral state: moving, not-moving, and sleep. The differences in median FRs were found for each treatment and behavioral state combination. A FR decrease was only found in the 2.0 g/kg EtOH treatment during not-moving states. However, robust decreases in FR variability were found across behavioral state in both the 1.0 and 2.0 g/kg EtOH treatment. Sleep was separately analyzed. EtOH modulated the UDS during sleep producing decreases in FRs. CONCLUSIONS: In conclusion, the changes in neural activity following EtOH administration in anesthetized animals are not conserved in awake-behaving animals. The most prominent difference following EtOH was a decrease in FR variability suggesting that acute EtOH may be affecting decision making via this mechanism.
背景:内侧前额皮质(mPFC)是一个参与评估和选择动机相关结果的大脑区域。mPFC 的神经活动在急性乙醇(EtOH)使用后发生改变,并且在啮齿动物模型中,低至 0.75 g/kg 的剂量就会导致认知缺陷。人们认为,急性 EtOH 后决策能力的下降至少部分是由于 mPFC 放电率(FR)的降低。然而,导致这一结论的数据仅在麻醉的啮齿动物中产生。本研究描述了急性 EtOH 注射对清醒行为啮齿动物 mPFC 神经活动的影响。
方法:进行了清醒行为和麻醉体内电生理记录。我们利用了 3 个组:第一组接受 2 次生理盐水注射,第二组接受 1.0 g/kg EtOH 注射,第三组接受生理盐水注射,然后接受 2 g/kg EtOH 注射。一周后,在麻醉记录中,先注射生理盐水,再注射 1.0 g/kg EtOH。
结果:麻醉状态下显示出神经活动的强烈减少和上下状态(UDS)动力学的差异。在清醒行为状态下,FR 根据行为状态进行分组:运动、非运动和睡眠。发现每个治疗和行为状态组合的中值 FR 差异。只有在 2.0 g/kg EtOH 治疗期间非运动状态下才发现 FR 下降。然而,在 1.0 和 2.0 g/kg EtOH 治疗下,在所有行为状态下都发现了 FR 变异性的显著降低。单独分析了睡眠。EtOH 在睡眠期间调节 UDS,导致 FR 下降。
结论:总之,麻醉动物中 EtOH 给药后神经活动的变化在清醒行为动物中并不保守。EtOH 后最显著的差异是 FR 变异性降低,表明急性 EtOH 可能通过这种机制影响决策。
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