Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Neurobiology, Northwestern University, Evanston, IL, USA.
Cell Rep. 2021 Nov 9;37(6):109975. doi: 10.1016/j.celrep.2021.109975.
Dopamine (DA) neurons in the ventral tier of the substantia nigra pars compacta (SNc) degenerate prominently in Parkinson's disease, while those in the dorsal tier are relatively spared. Defining the molecular, functional, and developmental characteristics of each SNc tier is crucial to understand their distinct susceptibility. We demonstrate that Sox6 expression distinguishes ventrally and dorsally biased DA neuron populations in the SNc. The Sox6 population in the ventral SNc includes an Aldh1a1 subset and is enriched in gene pathways that underpin vulnerability. Sox6 neurons project to the dorsal striatum and show activity correlated with acceleration. Sox6 neurons project to the medial, ventral, and caudal striatum and respond to rewards. Moreover, we show that this adult division is encoded early in development. Overall, our work demonstrates a dual origin of the SNc that results in DA neuron cohorts with distinct molecular profiles, projections, and functions.
腹侧被盖区（SNc）中的多巴胺（DA）神经元在帕金森病中明显退化，而背侧被盖区中的神经元则相对幸免。确定每个 SNc 层的分子、功能和发育特征对于了解它们的不同易感性至关重要。我们证明 Sox6 表达可区分 SNc 中的腹侧和背侧偏置 DA 神经元群体。腹侧 SNc 中的 Sox6 群体包括 Aldh1a1 亚群，并且富含支持脆弱性的基因途径。Sox6 神经元投射到背侧纹状体，并显示与加速相关的活动。Sox6 神经元投射到内侧、腹侧和尾状核状体，并对奖励做出反应。此外，我们表明这种成年分裂在早期发育中就已被编码。总的来说，我们的工作表明 SNc 具有双重起源，导致具有不同分子特征、投射和功能的 DA 神经元群体。
