Abstract：
The maturation of forebrain dopamine circuitry occurs over multiple developmental periods, extending from early postnatal life until adulthood, with the precise timing of maturation defined by the target region. We recently demonstrated in the adult mouse brain that axon terminals arising from midbrain dopamine neurons innervate the anterior corpus callosum and that oligodendrocyte lineage cells in this white matter tract express dopamine receptor transcripts. Whether corpus callosal dopamine circuitry undergoes maturational changes between early adolescence and adulthood is unknown but may be relevant to understanding the dramatic micro- and macro-anatomical changes that occur in the corpus callosum of multiple species during early adolescence, including in the degree of myelination. Using quantitative neuroanatomy, we show that dopamine innervation in the forceps minor, but not the rostral genu, of the corpus callosum, is greater during early adolescence (P21) compared to adulthood (>P90) in wild-type mice. We further demonstrate with RNAscope that, as in the adult, Drd1 and Drd2 transcripts are expressed at higher levels in oligodendrocyte precursor cells (OPCs) and decline as these cells differentiate into oligodendrocytes. In addition, the number of OPCs that express Drd1 transcripts during early adolescence is double the number of those expressing the transcript during early adulthood. These data further implicate dopamine in axon myelination and myelin regulation. Moreover, because developmental (activity-independent) myelination peaks during early adolescence, with experience-dependent (activity-dependent) myelination greatest during early adulthood, our data suggest that potential roles of dopamine on callosal myelination shift between early adolescence and adulthood, from a developmental role to an experience-dependent role.
摘要：
前脑多巴胺电路的成熟发生在多个发育期，从出生后的早期生活一直延伸到成年，成熟的精确时间由目标区域定义。我们最近在成年小鼠大脑中证明，中脑多巴胺神经元产生的轴突末端支配着call前部体，并且该白质束中的少突胶质细胞谱系细胞表达多巴胺受体转录本。在青春期早期和成年期之间，call体多巴胺回路是否经历成熟变化尚不清楚，但可能与了解青春期早期多种物种call体发生的戏剧性微观和宏观解剖变化有关，包括髓鞘形成的程度。使用定量神经解剖学，我们发现小镊子中的多巴胺神经支配，但不是头端的Genu，call体，在野生型小鼠中,在青春期早期(P21)相比于成年期(>P90)更大。我们用RNAscope进一步证明，就像成年人一样，Drdl和Drd2转录物在少突胶质细胞前体细胞(OPCs)中以较高的水平表达,并且随着这些细胞分化成少突胶质细胞而下降。此外,青春期早期表达Drd1转录本的OPCs数量是成年早期表达转录本的OPCs数量的两倍.这些数据进一步暗示多巴胺参与轴突髓鞘形成和髓鞘调节。此外，因为发育（活动无关）髓鞘形成在青春期早期达到高峰，在成年早期，经验依赖性（活动依赖性）髓鞘形成最大，我们的数据表明，多巴胺对call骨髓鞘形成的潜在作用在青春期早期和成年期之间转移，从发展角色到经验依赖角色。
