Taxier Lisa R, Neira Sofia, Flanigan Meghan E, Haun Harold L, Eberle Maya R, Kooyman Lili S, Markowitz Sloan Y, Kash Thomas L
Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599; Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
J Neurosci. 2025 Feb 26;45(9):e0525242024. doi: 10.1523/JNEUROSCI.0525-24.2024.
Blunted sensitivity to ethanol's aversive effects can increase motivation to consume ethanol; yet, the neurobiological circuits responsible for encoding these aversive properties are not fully understood. Plasticity in cells projecting from the anterior insular cortex (aIC) to the basolateral amygdala (BLA) is critical for taste aversion learning and retrieval, suggesting this circuit's potential involvement in modulating the aversive properties of ethanol. Here, we tested the hypothesis that GABAergic currents onto aIC→BLA projections would be facilitated as a consequence of retrieval of an ethanol-conditioned taste aversion (CTA). Consistent with this hypothesis, frequency of mIPSCs was increased 1 h following retrieval of an ethanol-CTA across cell layers in aIC→BLA projection neurons. This increase in GABAergic plasticity occurred in a circuit-specific, time-limited, and ethanol-CTA retrieval-dependent manner. Additionally, local inhibitory inputs onto layer 2/3 aIC→BLA projection neurons were greater in number and strength following ethanol-CTA. Finally, DREADD-mediated inhibition of aIC parvalbumin-expressing cells blunted the retrieval of ethanol-CTA in male, but not female, mice. Collectively, this work implicates a circuit-specific and memory retrieval-dependent increase in GABAergic tone following retrieval of an ethanol-CTA, thereby advancing our understanding of how the aversive effects of ethanol are encoded in the brain.
对乙醇厌恶效应的敏感性降低会增加乙醇消费动机；然而，负责编码这些厌恶特性的神经生物学回路尚未完全了解。从前岛叶皮质（aIC）投射到基底外侧杏仁核（BLA）的细胞可塑性对于味觉厌恶学习和恢复至关重要，这表明该回路可能参与调节乙醇的厌恶特性。在此，我们测试了一个假设，即乙醇条件性味觉厌恶（CTA）恢复后，aIC→BLA投射上的GABA能电流会增强。与该假设一致，在aIC→BLA投射神经元的各细胞层中，乙醇CTA恢复1小时后，微小抑制性突触后电流（mIPSCs）频率增加。这种GABA能可塑性的增加以回路特异性、时间限制和乙醇CTA恢复依赖性的方式发生。此外，乙醇CTA后，2/3层aIC→BLA投射神经元上的局部抑制性输入在数量和强度上更大。最后，设计受体只被激活的药物（DREADD）介导的对aIC中表达小白蛋白细胞的抑制减弱了雄性而非雌性小鼠中乙醇CTA的恢复。总的来说，这项工作表明乙醇CTA恢复后，GABA能张力会出现回路特异性和记忆恢复依赖性增加，从而增进了我们对乙醇厌恶效应在大脑中如何编码的理解。
