Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Program in Neuroscience, University of Maryland Baltimore, Baltimore, MD, 21201, USA.
Neuropharmacology. 2021 Sep 15;196:108695. doi: 10.1016/j.neuropharm.2021.108695. Epub 2021 Jul 4.
Modifications in brain regions that govern reward-seeking are thought to contribute to persistent behaviors that are heavily associated with alcohol-use disorder (AUD) including binge ethanol drinking. The bed nucleus of the stria terminalis (BNST) is a critical node linked to both alcohol consumption and the onset, maintenance and progression of adaptive anxiety and stress-related disorders. Differences in anatomy, connectivity and receptor subpopulations, make the BNST a sexually dimorphic region. Previous work indicates that the ventral BNST (vBNST) receives input from the insular cortex (IC), a brain region involved in processing the body's internal state. This IC-vBNST projection has also been implicated in emotional and reward-seeking processes. Therefore, we examined the functional properties of vBNST-projecting, IC neurons in male and female mice that have undergone short-term ethanol exposure and abstinence using a voluntary Drinking in the Dark paradigm (DID) paired with whole-cell slice electrophysiology. First we show that IC neurons projected predominantly to the vBNST. Next, our data show that short-term ethanol exposure and abstinence enhanced excitatory synaptic strength onto vBNST-projecting, IC neurons in both sexes. However, we observed diametrically opposing modifications in excitability across sexes. In particular, short-term ethanol exposure resulted in increased intrinsic excitability of vBNST-projecting, IC neurons in females but not in males. Furthermore, in females, abstinence decreased the excitability of these same neurons. Taken together these findings show that short-term ethanol exposure, as well as the abstinence cause sex-related adaptations in BNST-projecting, IC neurons.
大脑中控制奖励寻求的区域的变化被认为是导致与酒精使用障碍（AUD）相关的持续行为的原因，包括 binge 乙醇饮酒。终纹床核（BNST）是一个关键节点，与酒精消费以及适应性焦虑和与应激相关的障碍的发生、维持和进展有关。解剖学、连接和受体亚群的差异使 BNST 成为一个性别二态性区域。以前的工作表明，腹侧 BNST（vBNST）接收来自岛叶皮层（IC）的输入，IC 是一个参与处理身体内部状态的大脑区域。该 IC-vBNST 投射也与情绪和奖励寻求过程有关。因此，我们使用自愿性暗饮范式（DID）结合全细胞切片电生理学，检查了在雄性和雌性小鼠中经历短期乙醇暴露和禁欲后，vBNST 投射的 IC 神经元的功能特性。首先，我们表明 IC 神经元主要投射到 vBNST。接下来，我们的数据表明，短期乙醇暴露和禁欲增强了两性 vBNST 投射的 IC 神经元的兴奋性突触强度。然而，我们观察到两性之间的兴奋性存在截然相反的变化。特别是，短期乙醇暴露导致雌性 vBNST 投射的 IC 神经元的内在兴奋性增加，但在雄性中则没有。此外，在雌性中，禁欲降低了这些相同神经元的兴奋性。总之，这些发现表明，短期乙醇暴露以及禁欲会导致 BNST 投射的 IC 神经元出现性别相关的适应性变化。
