Different electrophysiological profiles of genetically labelled dopaminergic neurons in the mouse midbrain and olfactory bulb
Different electrophysiological profiles of genetically labelled dopaminergic neurons in the mouse midbrain and olfactory bulb
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DOI：
10.1111/ejn.16239
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发表时间：
2024-01-02
影响因子：
3.4
通讯作者：
Galliano，Elisa
中科院分区：
文献类型：
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作者：
Lau，Maggy Yu Hei;Gadiwalla，Sana;Galliano，Elisa
多巴胺（DA）神经元在多种脑功能中发挥关键作用，包括运动、奖赏处理和感觉知觉。DA神经元在中脑（黑质背侧部[SNC]和中脑被盖区[VTA]）和前脑的嗅球（OB）中最丰富。有趣的是，OB DA神经元的一个亚型能够在整个生命中再生，而第二类仅在胚胎发育期间出生。SNC和VTA的令人信服的证据也表明在形态，连接和功能方面存在很大的异质性。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，我们在来自幼年DAT‐tdTomato小鼠的离体脑切片中进行了免疫组织化学和全细胞膜片钳记录。在确定了多巴胺转运蛋白（DAT）Cre的特异性和特异性后，我们比较了中脑和前脑延髓DA亚型的索马形状、被动膜特性、电压下降和动作电位（AP）放电。我们发现，中脑和OB内的每个DA亚组是高度异质性的，并且两个脑区的DA神经元也有很大的不同。这些发现补充了先前在大鼠中的工作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。
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.