Contrasting sex-dependent adaptations to synaptic physiology and membrane properties of prefrontal cortex interneuron subtypes in a mouse model of binge drinking.
Contrasting sex-dependent adaptations to synaptic physiology and membrane properties of prefrontal cortex interneuron subtypes in a mouse model of binge drinking.
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DOI：
10.1016/j.neuropharm.2020.108126
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发表时间：
2020-11-01
影响因子：
4.7
通讯作者：
Conn PJ
中科院分区：
文献类型：
--
作者：
Joffe ME;Winder DG;Conn PJ
酒精使用障碍（AUD）影响所有性别，但患有AUD的女性可能特别容易受到渴望和其他疾病成分的影响。虽然许多大脑区域都与AUD病因有关，但适当的前额皮质（PFC）功能对于自上而下的渴望管理和饮酒行为的调节尤为重要。PFC输出的基本调节是由局部抑制性中间神经元提供的，然而饮酒如何影响中间神经元生理仍然知之甚少，特别是在女性个体中。为了解决这一空白，我们建立了荧光报告基因小鼠，根据小白蛋白（PV-IN）或生长抑素（SST-IN）的表达来标记深层边缘前PFC的两大类中间神经元。然后，我们在啮齿动物狂饮模型中询问PV-IN和SST-IN膜和突触生理学。从青春期晚期开始，小鼠接受3-4周的间歇摄入（IA）乙醇。我们在最后一次饮酒后的第二天准备了急性脑切片。与对照组相比，IA乙醇小鼠的PV-INs而非SST-INs表现出更高的兴奋性，无论性别如何。相反，对PV-INs的突触适应因性别而异。虽然饮酒会降低雌性小鼠对PV-INs的兴奋性突触强度，但相对于对照组，IA乙醇雄性小鼠的PV-INs表现出增强的兴奋性传递。相比之下，在所有小鼠中，IA乙醇均观察到SST-INs上的突触强度下降。总之，这些发现说明了饮酒相关PFC病理生理上的新的性别差异。发现恢复长期饮酒后PV-IN和SST-IN功能障碍的方法，为所有AUD患者开发新的治疗方法提供了机会。
Alcohol use disorder (AUD) affects all sexes, however women who develop AUD may be particularly susceptible to cravings and other components of the disease. While many brain regions are involved in AUD etiology, proper prefrontal cortex (PFC) function is particularly important for top-down craving management and the moderation of drinking behaviors. Essential regulation of PFC output is provided by local inhibitory interneurons, yet how drinking affects interneuron physiology remains poorly understood, particularly in female individuals. To address this gap, we generated fluorescent reporter transgenic mice to label the two major classes of interneuron in deep layer prelimbic PFC, based on expression of parvalbumin (PV-IN) or somatostatin (SST-IN). We then interrogated PV-IN and SST-IN membrane and synaptic physiology in a rodent model of binge drinking. Beginning in late adolescence, mice received 3-4 weeks of intermittent access (IA) ethanol. We prepared acute brain slices one day after the last drinking session. PV-INs but not SST-INs from IA ethanol mice displayed increased excitability relative to controls, regardless of sex. On the contrary, synaptic adaptations to PV-INs differed based on sex. While drinking decreased excitatory synaptic strength onto PV-INs from female mice, PV-INs from IA ethanol male mice exhibited potentiated excitatory transmission relative to controls. In contrast, decreased synaptic strength onto SST-INs was observed following IA ethanol in all groups of mice. Together, these findings illustrate novel sex differences in drinking-related PFC pathophysiology. Discovering means to restore PV-IN and SST-IN dysfunction following extended drinking provides opportunities for developing new treatments for all AUD patients.
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影响因子：
2.3
作者：
Gross, WC;Billingham, RE
通讯作者：
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通讯作者：
Nicoletti F