PDF(Pubmed)
Abstract：
BACKGROUND: Alcohol is commonly consumed by adolescents in a binge-like pattern, which can lead to long-lasting cognitive deficits, including reduced behavioral flexibility. We and others have determined that adolescent intermittent ethanol (AIE) exposure leads to increased number of perineuronal net (PNN) numbers in brain regions that are important for behavioral flexibility. However, whether altered neurochemistry stemming from AIE exposure plays a significant role in reduced behavioral flexibility is unknown.
METHODS: We measured the number and size of parvalbumin expressing (PV+) interneurons and associated PNNs within the orbitofrontal cortex (OFC), prelimbic cortex (PrL), infralimbic cortex (IL), and anterior insular cortex (AIC) of female and male rats following AIE or control exposure and subsequent training on an attentional set-shift task (ASST). We then ran analyses to determine whether AIE-induced changes in PV and PNN measures statistically mediated the AIE-induced behavioral deficit in reversal learning.
RESULTS: We demonstrate that AIE exposure impaired behavioral flexibility on reversal two of the ASST (i.e., recalling the initial learned associations), and led to smaller PV+ cells and increased PNN numbers in the AIC. Interestingly, PNN size and number were not altered in the PrL or IL following AIE exposure, in contrast to prior reports. Mediation analyses suggest that AIE alters behavioral flexibility, at least in part through changes in PV and PNN fluorescent measures in the AIC.
CONCLUSIONS: This study reveals a significant link between AIE exposure, neural alterations, and diminished behavioral flexibility in rats, and highlights a potential novel mechanism comprising changes in PV and PNN measures within the AIC. Future studies should explore the impact of PNN degradation within the AIC on behavioral flexibility.
METHODS: We measured the number and size of parvalbumin expressing (PV+) interneurons and associated PNNs within the orbitofrontal cortex (OFC), prelimbic cortex (PrL), infralimbic cortex (IL), and anterior insular cortex (AIC) of female and male rats following AIE or control exposure and subsequent training on an attentional set-shift task (ASST). We then ran analyses to determine whether AIE-induced changes in PV and PNN measures statistically mediated the AIE-induced behavioral deficit in reversal learning.
RESULTS: We demonstrate that AIE exposure impaired behavioral flexibility on reversal two of the ASST (i.e., recalling the initial learned associations), and led to smaller PV+ cells and increased PNN numbers in the AIC. Interestingly, PNN size and number were not altered in the PrL or IL following AIE exposure, in contrast to prior reports. Mediation analyses suggest that AIE alters behavioral flexibility, at least in part through changes in PV and PNN fluorescent measures in the AIC.
CONCLUSIONS: This study reveals a significant link between AIE exposure, neural alterations, and diminished behavioral flexibility in rats, and highlights a potential novel mechanism comprising changes in PV and PNN measures within the AIC. Future studies should explore the impact of PNN degradation within the AIC on behavioral flexibility.
摘要：
背景：青少年通常以暴饮暴食的方式饮酒，这可能导致长期的认知缺陷，包括行为灵活性的降低。我们和其他人已经确定，青少年间歇性乙醇（AIE）暴露会导致大脑区域的神经周网络（PNN）数量增加，这对行为灵活性很重要。然而,AIE暴露引起的神经化学改变是否在行为灵活性降低中起重要作用尚不清楚.
方法：我们测量了眶额叶皮质（OFC）内表达小白蛋白（PV）中间神经元和相关PNN的数量和大小，前边缘皮质(PrL),外缘皮质(IL),在AIE或对照暴露以及随后的注意力转移任务（ASST）训练后，雌性和雄性大鼠的前岛叶皮层（AIC）。然后，我们进行了分析，以确定AIE引起的PV和PNN变化是否在统计学上介导了AIE引起的逆转学习行为缺陷。
结果：我们证明了AIE暴露会损害ASST逆转两个时的行为灵活性（即，回顾最初的学习关联)，并导致AIC中PV+电池变小，PNN数量增加。有趣的是,暴露于AIE后，PrL或IL中的PNN大小和数量没有改变，与以前的报告相反。中介分析表明，AIE改变了行为灵活性，至少部分通过AIC中PV和PNN荧光测量的变化。
结论：这项研究揭示了AIE暴露之间的重要联系，神经改变，老鼠的行为灵活性减弱，并强调了一个潜在的新机制，包括AIC内PV和PNN测量的变化。未来的研究应该探索AIC内PNN退化对行为灵活性的影响。
方法：我们测量了眶额叶皮质（OFC）内表达小白蛋白（PV）中间神经元和相关PNN的数量和大小，前边缘皮质(PrL),外缘皮质(IL),在AIE或对照暴露以及随后的注意力转移任务（ASST）训练后，雌性和雄性大鼠的前岛叶皮层（AIC）。然后，我们进行了分析，以确定AIE引起的PV和PNN变化是否在统计学上介导了AIE引起的逆转学习行为缺陷。
结果：我们证明了AIE暴露会损害ASST逆转两个时的行为灵活性（即，回顾最初的学习关联)，并导致AIC中PV+电池变小，PNN数量增加。有趣的是,暴露于AIE后，PrL或IL中的PNN大小和数量没有改变，与以前的报告相反。中介分析表明，AIE改变了行为灵活性，至少部分通过AIC中PV和PNN荧光测量的变化。
结论：这项研究揭示了AIE暴露之间的重要联系，神经改变，老鼠的行为灵活性减弱，并强调了一个潜在的新机制，包括AIC内PV和PNN测量的变化。未来的研究应该探索AIC内PNN退化对行为灵活性的影响。
