美国斯坦福大学Michelle Monje小组发现，阿片类药物奖赏需要腹侧被盖区的髓鞘可塑性。该研究于2024年6月5日在线发表于国际一流学术期刊《自然》。

研究人员探讨了髓鞘可塑性在多巴胺能回路和奖赏学习中的作用。研究人员证明，多巴胺能神经元活动调节的髓鞘可塑性是多巴胺能回路功能和阿片类物质奖赏的关键调节因子。多巴胺能神经元的光遗传刺激、GABA能神经元的光遗传抑制或吗啡的施用诱发了多巴胺能神经元的活动，而少突胶质细胞系对多巴胺能神经元的活动做出了反应。

这些少突胶质细胞的变化选择性地在腹侧被盖区表现明显，但不沿内侧前脑束轴突投射，也不在目标核内。对少突胶质细胞生成的遗传阻断抑制了伏隔核的多巴胺释放动态，并损害了对吗啡的行为调节。综上所述，这些发现强调了少突胶质细胞在奖赏学习中的关键作用，并确定多巴胺能神经元活动调节的髓鞘可塑性是阿片类药物奖赏所需的重要回路修改。

据了解，所有滥用药物都会引起突触传递和神经回路功能的长期变化，而这些变化正是药物滥用症的基础。神经回路可塑性的另一个新近受到重视的机制是通过活动调节的髓鞘变化来实现的，这种变化可以调整神经回路功能并影响认知行为。

附：英文原文

Title: Myelin plasticity in the ventral tegmental area is required for opioid reward

Author: Yaln, Belgin, Pomrenze, Matthew B., Malacon, Karen, Drexler, Richard, Rogers, Abigail E., Shamardani, Kiarash, Chau, Isabelle J., Taylor, Kathryn R., Ni, Lijun, Contreras-Esquivel, Daniel, Malenka, Robert C., Monje, Michelle

Issue&Volume: 2024-06-05

Abstract: All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance-use disorders1,2. Another recently appreciated mechanism of neural circuit plasticity is mediated through activity-regulated changes in myelin that can tune circuit function and influence cognitive behaviour3,4,5,6,7. Here we explore the role of myelin plasticity in dopaminergic circuitry and reward learning. We demonstrate that dopaminergic neuronal activity-regulated myelin plasticity is a key modulator of dopaminergic circuit function and opioid reward. Oligodendroglial lineage cells respond to dopaminergic neuronal activity evoked by optogenetic stimulation of dopaminergic neurons, optogenetic inhibition of GABAergic neurons, or administration of morphine. These oligodendroglial changes are evident selectively within the ventral tegmental area but not along the axonal projections in the medial forebrain bundle nor within the target nucleus accumbens. Genetic blockade of oligodendrogenesis dampens dopamine release dynamics in nucleus accumbens and impairs behavioural conditioning to morphine. Taken together, these findings underscore a critical role for oligodendrogenesis in reward learning and identify dopaminergic neuronal activity-regulated myelin plasticity as an important circuit modification that is required for opioid reward.

DOI: 10.1038/s41586-024-07525-7

Source: https://www.nature.com/articles/s41586-024-07525-7