CUNY Neuroscience Collaborative, The Graduate Center, City University of New York, New York, NY, USA.
Department of Biology, College of Staten Island, City University of New York, Staten Island, NY, USA.
Eur J Neurosci. 2024 May;59(10):2535-2548. doi: 10.1111/ejn.16385. Epub 2024 May 8.
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.
大脑前额叶多巴胺回路的成熟发生在多个发育阶段，从出生后早期一直持续到成年期，其精确的成熟时间由目标区域决定。我们最近在成年小鼠大脑中证明，从中脑多巴胺神经元发出的轴突末梢支配胼胝体前部，而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。从中幼年到成年，胼胝体多巴胺回路是否会发生成熟变化尚不清楚，但这可能与理解多种物种在中幼年期间胼胝体发生的剧烈微观和宏观解剖变化有关，包括髓鞘化程度。使用定量神经解剖学方法，我们发现，在野生型小鼠中，与成年（>P90）相比，幼年（P21）时，胼胝体小钳（forceps minor）而非前连合（rostral genu）的多巴胺支配更多。我们进一步通过 RNAscope 显示，与成年时一样，Drd1 和 Drd2 转录本在少突胶质细胞前体细胞（OPC）中表达水平更高，并随着这些细胞分化为少突胶质细胞而下降。此外，在幼年时期表达 Drd1 转录本的 OPC 数量是表达该转录本的成年早期 OPC 数量的两倍。这些数据进一步表明多巴胺参与轴突髓鞘形成和髓鞘调节。此外，由于发育（非活动依赖）髓鞘化在中幼年达到高峰，而经验依赖（活动依赖）髓鞘化在成年早期达到高峰，我们的数据表明，多巴胺在胼胝体髓鞘化中的潜在作用从中幼年到成年发生转变，从发育作用转变为经验依赖作用。
