Dopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta [SNC] and Ventral Tegmental Area [VTA]) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Compelling evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain bulbar DA neurons, we performed immunohistochemistry and whole-cell patch-clamp recordings in ex vivo brain slices from juvenile DAT-tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential (AP) firing across midbrain and forebrain bulbar DA subtypes. We found that each DA subgroup within midbrain and OB was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression and in vivo datasets, further questioning the existence of a single “dopaminergic” neuronal phenotype.

中文翻译：

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小鼠中脑和嗅球中基因标记的多巴胺能神经元的不同电生理特征

多巴胺能 (DA) 神经元在多种大脑功能中发挥着关键作用，包括运动、奖励处理和感官知觉。 DA 神经元在中脑（黑质致密部 [SNC] 和腹侧被盖区 [VTA]）和前脑的嗅球 (OB) 中最为丰富。有趣的是，OB DA 神经元的一个亚型能够在一生中再生，而第二个亚型则完全在胚胎发育期间诞生。 SNC 和 VTA 中令人信服的证据也表明在形态、连接性和功能方面存在显着的异质性。为了进一步研究这种异质性并直接比较中脑和前脑延髓 DA 神经元的形式和功能，我们对幼年 DAT-tdTomato 小鼠的离体脑切片进行了免疫组织化学和全细胞膜片钳记录。在确认多巴胺转运蛋白 (DAT) Cre 线的外显率和特异性后，我们比较了中脑和前脑延髓 DA 亚型的体细胞形状、被动膜特性、电压骤降和动作电位 (AP) 放电。我们发现中脑和 OB 内的每个 DA 亚群都具有高度异质性，并且两个大脑区域的 DA 神经元也存在显着差异。这些发现补充了之前在大鼠中的研究以及基因表达和体内数据集，进一步质疑单一“多巴胺能”神经元表型的存在。