PDF(Pubmed)
Abstract：
The prefrontal cortex (PFC) regulates drinking behaviors and affective changes following chronic alcohol use. PFC activity is dynamically modulated by local inhibitory interneurons (INs), which can be divided into non-overlapping groups with distinct functional roles. Within deeper layers of neocortex, INs that express either parvalbumin or somatostatin directly inhibit pyramidal cells. By contrast, the plurality of all remaining INs express vasoactive intestinal peptide (VIP), reside within superficial layers, and preferentially target other types of INs. While recent studies have described adaptations to PFC parvalbumin-INs and somatostatin-INs in alcohol use models, whether ethanol or drinking affect the physiology of PFC VIP-INs has not been reported. To address this gap, we used genetically engineered female and male mice to target VIP-INs in layers 1-3 of prelimbic PFC for whole-cell patch-clamp electrophysiology. We found that ethanol (20 mM, ∼0.09 BEC/90 mg/dL) application to PFC brain slices enhances VIP-IN excitability. We next examined effects following chronic drinking by providing mice with 4 weeks of intermittent access (IA) ethanol two-bottle choice in the home cage. In these studies, VIP-INs from female and male IA ethanol mice displayed reduced excitability relative to cells from water-only controls. Finally, we assessed whether these effects continue into abstinence. After 7-13 days without ethanol, the hypo-excitability of VIP-INs from male IA ethanol mice persisted, whereas cells from female IA ethanol mice were not different from their controls. Together, these findings illustrate that acute ethanol enhances VIP-IN excitability and suggest these cells undergo pronounced homeostatic changes following long-term drinking.
摘要：
前额叶皮质（PFC）调节长期饮酒后的饮酒行为和情感变化。PFC活性由局部抑制性中间神经元(IN)动态调节，可以分为具有不同功能角色的非重叠组。在新皮层的深层，表达小白蛋白或生长抑素的INs直接抑制锥体细胞。相比之下,所有剩余的INs中的多个表达血管活性肠肽(VIP)，驻留在表层内，并优先针对其他类型的INs。虽然最近的研究已经描述了在酒精使用模型中对PFC小白蛋白-INs和生长抑素-INs的适应，乙醇或饮酒是否影响PFCVIP-INs的生理尚未报道。为了解决这个差距，我们使用基因工程的雌性和雄性小鼠靶向前边缘PFC层1-3中的VIP-INs用于全细胞膜片钳电生理学。我们发现乙醇(20mM，〜0.09BEC/90mg/dL）应用于PFC脑片可增强VIP-IN兴奋性。接下来，我们通过在笼子中为小鼠提供4周的间歇性获取（IA）乙醇两瓶选择来检查长期饮酒后的影响。在这些研究中,来自雌性和雄性IA乙醇小鼠的VIP-IN相对于来自仅水对照的细胞显示出降低的兴奋性。最后,我们评估了这些影响是否持续到禁欲。7-13天后无乙醇，雄性IA乙醇小鼠VIP-INs的低兴奋性持续存在，而来自雌性IA乙醇小鼠的细胞与对照组没有差异。一起,这些研究结果表明,急性乙醇可增强VIP-IN的兴奋性,并提示这些细胞在长期饮酒后发生明显的稳态变化.
