Department of Neuroscience, Charleston Alcohol Research Center, Medical University of South Carolina, Charleston, SC 29425.
Department of Neuroscience, Charleston Alcohol Research Center, Medical University of South Carolina, Charleston, SC 29425
eNeuro. 2020 Jun 19;7(3). doi: 10.1523/ENEURO.0077-20.2020. Print 2020 May/Jun.
Alcohol (ethanol) use disorder is associated with changes in frontal cortical areas including the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) that contribute to cognitive deficits, uncontrolled drinking, and relapse. Acute ethanol exposure reduces intrinsic excitability of lateral OFC (lOFC) neurons, while chronic exposure and long-term drinking influence plasticity of intrinsic excitability and function of glutamatergic synapses. However, the time course that these adaptations occur across a history of ethanol drinking is unknown. The current study examined whether short-term and long-term voluntary ethanol consumption using an intermittent access paradigm would alter the biophysical properties of deep-layer pyramidal neurons in the ACC and lOFC. Neuronal spiking varied in the ACC with an initial increase in evoked firing after 1 d of drinking followed by a decrease in firing in mice that consumed ethanol for one week. No difference in lOFC spike number was observed between water controls and 1-d ethanol drinking mice, but mice that consumed ethanol for one week or more showed a significant increase in evoked firing. Voluntary ethanol drinking for 4 weeks also produced a total loss of ethanol inhibition of lOFC neurons. There was no effect of drinking on excitatory or inhibitory synaptic events in ACC or lOFC neurons across all time points in this model. Overall, these results demonstrate that voluntary drinking alters neuronal excitability in the ACC and lOFC in distinct ways and on a different time scale that may contribute to the impairment of prefrontal cortex-dependent behaviors observed in individuals with alcohol use disorder (AUD).
酒精（乙醇）使用障碍与额皮质区域的变化有关，包括前扣带皮层（ACC）和眶额皮层（OFC），这些区域导致认知缺陷、无法控制的饮酒和复发。急性乙醇暴露会降低外侧 OFC（lOFC）神经元的内在兴奋性，而慢性暴露和长期饮酒会影响内在兴奋性和谷氨酸能突触功能的可塑性。然而，这些适应在饮酒史中发生的时间过程尚不清楚。本研究使用间歇接触范式检查了短期和长期自愿饮酒是否会改变 ACC 和 lOFC 中深层锥体神经元的生物物理特性。在 ACC 中，神经元的爆发随着饮酒 1 天后诱发放电的初始增加而变化，然后在饮酒 1 周的小鼠中放电减少。在水对照组和 1 天乙醇饮酒小鼠之间，未观察到 lOFC 尖峰数的差异，但饮酒 1 周或更长时间的小鼠表现出诱发放电的显著增加。自愿饮酒 4 周也导致 lOFC 神经元对乙醇的抑制完全丧失。在该模型的所有时间点，饮酒对 ACC 或 lOFC 神经元的兴奋性或抑制性突触事件均无影响。总的来说，这些结果表明，自愿饮酒以不同的方式和不同的时间尺度改变了 ACC 和 lOFC 中的神经元兴奋性，这可能导致在酒精使用障碍（AUD）个体中观察到的前额叶皮层依赖行为的损伤。
