Ventral tegmental area GABA, glutamate, and glutamate‐GABA neurons are heterogeneous in their electrophysiological and pharmacological properties,European Journal of Neuroscience

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Ventral tegmental area GABA, glutamate, and glutamate‐GABA neurons are heterogeneous in their electrophysiological and pharmacological properties
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2021-02-22 , DOI: 10.1111/ejn.15156
Jorge Miranda‐Barrientos ₁ , Ian Chambers ₁ , Smriti Mongia ₁ , Bing Liu ₁ , Hui‐Ling Wang ₁ , Gabriel E Mateo‐Semidey ₁ , Elyssa B Margolis ₂ , Shiliang Zhang ₃ , Marisela Morales ₁

Affiliation

The ventral tegmental area (VTA) contains dopamine neurons intermixed with GABA‐releasing (expressing vesicular GABA transporter, VGaT), glutamate‐releasing (expressing vesicular glutamate transporter 2, VGluT2), and glutamate‐GABA co‐releasing (co‐expressing VGluT2 and VGaT) neurons. By delivering INTRSECT viral vectors into the VTA of double vglut2‐Cre/vgat‐Flp transgenic mice, we targeted specific VTA cell populations for ex vivo recordings. We found that VGluT2⁺ VGaT⁻ and VGluT2⁺ VGaT⁺ neurons on average had relatively hyperpolarized resting membrane potential, greater rheobase, and lower spontaneous firing frequency compared to VGluT2⁻ VGaT⁺ neurons, suggesting that VTA glutamate‐releasing and glutamate‐GABA co‐releasing neurons require stronger excitatory drive to fire than GABA‐releasing neurons. In addition, we detected expression of Oprm1mRNA (encoding µ opioid receptors, MOR) in VGluT2⁺ VGaT⁻ and VGluT2⁻ VGaT⁺ neurons, and that the MOR agonist DAMGO hyperpolarized neurons with these phenotypes. Collectively, we demonstrate the utility of the double transgenic mouse to access VTA glutamate, glutamate‐GABA, and GABA neurons to determine their electrophysiological properties.

中文翻译：

腹侧被盖区GABA，谷氨酸和谷氨酸-GABA神经元在其电生理和药理特性方面是异质的

腹侧被盖区（VTA）包含与GABA释放（表达水泡GABA转运蛋白，VGaT），谷氨酸释放（表达水泡谷氨酸转运蛋白2，VGluT2）和谷氨酸-GABA共同释放（共表达VGluT2和VGaT）神经元。通过将INTRSECT病毒载体送入双vglut2-Cre / vgat-Flp转基因小鼠的VTA中，我们靶向特定的VTA细胞群体进行离体记录。我们发现，VGLUT2 ⁺ VGaT ^-和VGLUT2 ⁺ VGaT ⁺此前平均神经元超极化相对静息电位，更大的rheobase，并降低自发放电频率相比VGLUT2 ^- VGaT ⁺神经元，提示VTA释放谷氨酸和GABA共同释放的神经元比释放GABA的神经元需要更强的兴奋激发力。此外，我们检测Oprm1mRNA的表达（编码μ阿片受体，MOR）在VGLUT2 ⁺ VGaT ^-和VGLUT2 ^- VGaT ⁺神经元，并且该MOR激动剂DAMGO超极化与这些表型神经元。我们共同证明了双转基因小鼠访问VTA谷氨酸，谷氨酸-GABA和GABA神经元以确定其电生理特性的效用。

更新日期：2021-04-08

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