Perineuronal nets in the insula regulate aversion-resistant alcohol drinking
Perineuronal nets in the insula regulate aversion-resistant alcohol drinking
复制标题
DOI：
10.1111/adb.12821
复制
发表时间：
2019-08-21
影响因子：
3.4
通讯作者：
Lasek, Amy W.
中科院分区：
文献类型：
--
作者：
Chen, Hu;Lasek, Amy W.
酒精使用障碍最有害的特征之一是，尽管有负面后果，但仍然强迫饮酒。岛叶皮层控制着在风险或冲突条件下的决策。皮质活动由抑制性中间神经元严格控制，所述抑制性中间神经元通常被称为神经元周网（PNN）的专门细胞外基质结构包围，所述PNN调节神经元的兴奋性和可塑性。PNNs的密度在反复暴饮暴食后增加，这表明它们可能在从社交到强迫性或厌恶性饮酒的过渡中发挥作用。在这里，我们研究了是否岛屿PNNs发挥作用，在厌恶性饮酒使用小鼠模型，其中乙醇掺杂苦味tastant奎宁。破坏PNNs使小鼠对奎宁掺杂的乙醇更敏感，而不是单独的乙醇。激活的c-fos的表达，作为衡量，发生在厌恶性饮酒，并进一步增强消除PNNs。这些结果表明，PNNs控制的激活厌恶抗饮酒期间，并建议适当的兴奋/抑制平衡是重要的冲突条件下的决策。破坏大脑中的PNN或优化大脑中的激活可能是减少厌恶性饮酒的一种新策略。
One of the most pernicious characteristics of alcohol use disorder is the compulsion to drink despite negative consequences. The insular cortex controls decision making under conditions of risk or conflict. Cortical activity is tightly controlled by inhibitory interneurons that are often enclosed by specialized extracellular matrix structures known as perineuronal nets (PNNs), which regulate neuronal excitability and plasticity. The density of PNNs in the insula increases after repeated bouts of binge drinking, suggesting that they may play a role in the transition from social to compulsive, or aversion-resistant, drinking. Here, we investigated whether insular PNNs play a role in aversion-resistant alcohol drinking using a mouse model in which ethanol was adulterated with the bitter tastant quinine. Disrupting PNNs in the insula rendered mice more sensitive to quinine-adulterated ethanol but not ethanol alone. Activation of the insula, as measured by c-fos expression, occurred during aversion-resistant drinking and was further enhanced by elimination of PNNs. These results demonstrate that PNNs control the activation of the insula during aversion-resistant drinking and suggest that proper excitatory/inhibitory balance is important for decision making under conditions of conflict. Disrupting PNNs in the insula or optimizing insula activation may be a novel strategy to reduce aversion-resistant drinking