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

• 成果类型: Article
• 署名作者: Yalcin, 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
• 署名单位: Stanford University; Stanford University; Howard Hughes Medical Institute
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5259
• DOI: 10.1038/s41586-024-07525-7
• 发表日期: 2024-06-20
• 页码: 677-685
• 关键词: dependent myelination; dopamine; neurons; identification; aversion; stress

摘要

All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance-use disorders 1,2 . Another recently appreciated mechanism of neural circuit plasticity is mediated through activity-regulated changes in myelin that can tune circuit function and influence cognitive behaviour 3-7 . 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. Oligodendrogenesis is shown to be involved in reward learning, with dopaminergic neuronal activity-regulated myelin plasticity being an important reward circuit modification.