Thompson Shannon M, Ferranti Anthony S, Joffe Max E
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
Translational Neuroscience Program, University of Pittsburgh, Pittsburgh, PA.
bioRxiv. 2023 Mar 10:2023.03.07.531614. doi: 10.1101/2023.03.07.531614.
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) 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 7-11 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.
前额叶皮层（PFC）调节慢性酒精使用后的饮酒行为和情感变化。PFC的活动受到局部抑制性中间神经元（INs）的动态调节，这些中间神经元可分为具有不同功能作用的不重叠组。在新皮层较深的层中，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，所有其余INs中的大多数表达血管活性肠肽（VIP），位于表层，并优先靶向其他类型的INs。虽然最近的研究描述了酒精使用模型中PFC小白蛋白-INs和生长抑素-INs的适应性变化，但乙醇或饮酒是否会影响PFC VIP-INs的生理学尚未见报道。为了填补这一空白，我们使用基因工程的雌性和雄性小鼠，将前边缘PFC第1-3层中的VIP-INs作为全细胞膜片钳电生理学的靶点。我们发现，将乙醇（20 mM，约0.09 BEC）应用于PFC脑片可增强VIP-INs的兴奋性。接下来，我们通过在饲养笼中为小鼠提供4周的间歇性接触（IA）乙醇两瓶选择，研究了慢性饮酒后的影响。在这些研究中，来自雌性和雄性IA乙醇小鼠的VIP-INs相对于仅饮水对照组的细胞表现出兴奋性降低。最后，我们评估了这些影响是否会持续到戒酒期。在没有乙醇的7-11天后，雄性IA乙醇小鼠的VIP-INs的低兴奋性持续存在，而雌性IA乙醇小鼠的细胞与对照组没有差异。总之，这些发现表明急性乙醇可增强VIP-INs的兴奋性，并提示这些细胞在长期饮酒后会发生明显的稳态变化。
