Ventral tegmental area GABA, glutamate, and glutamate-GABA neurons are heterogeneous in their electrophysiological and pharmacological properties.
Ventral tegmental area GABA, glutamate, and glutamate-GABA neurons are heterogeneous in their electrophysiological and pharmacological properties.
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DOI：
10.1111/ejn.15156
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发表时间：
2021-02-22
期刊：
影响因子：
--
通讯作者：
Morales M
中科院分区：
文献类型：
--
作者：
Miranda-Barrientos J;Chambers I;Mongia S;Liu B;Wang HL;Mateo-Semidey GE;Margolis EB;Zhang S;Morales M
腹侧被盖区（VTA）含有与GABA释放（表达囊泡GABA转运体，VGaT）、谷氨酸释放（表达囊泡谷氨酸转运体2，VGluT2）和谷氨酸-GABA共释放（共表达VGaT和VGluT2）神经元混合的多巴胺神经元。通过将INTRSECT病毒载体递送到双vT2-Cre/vgat-Flp转基因小鼠的VTA中，我们靶向特定的VTA细胞群体用于离体记录。我们发现，与VGluT2 − VGaT+神经元相比，VGluT2 + VGaT −和VGluT2 + VGaT+神经元平均具有相对超极化的静息膜电位，更大的基强度和更低的自发放电频率，这表明VTA谷氨酸释放神经元和谷氨酸-GABA共释放神经元需要比GABA释放神经元更强的兴奋性驱动来放电。此外，我们检测到Oprm1 mRNA（编码μ阿片受体，莫尔）在VGluT2 + VGaT −和VGluT2 − VGaT+神经元中的表达，并且莫尔激动剂DAMGO使具有这些表型的神经元超极化。总的来说，我们证明了双转基因小鼠的实用性，以访问腹侧被盖区谷氨酸，谷氨酸-GABA和GABA神经元，以确定其电生理特性。腹侧被盖区谷氨酸-GABA共释放神经元在其生理特性方面是多样的，并且与腹侧被盖区谷氨酸释放神经元和GABA释放神经元共享这些特性中的一些。μ-阿片受体激活使一些VTA谷氨酸释放神经元和一些GABA释放神经元超极化。
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 VGaT and VGluT2) 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. VTA glutamate-GABA co-releasing neurons are diverse in their physiological properties and share some of those properties with VTA glutamate-releasing and GABA-releasing neurons. μ-opioid receptor activation hyperpolarizes some VTA glutamate-releasing and some GABA-releasing neurons.
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影响因子：
8.8
作者：
Root DH;Barker DJ;Estrin DJ;Miranda-Barrientos JA;Liu B;Zhang S;Wang HL;Vautier F;Ramakrishnan C;Kim YS;Fenno L;Deisseroth K;Morales M
通讯作者：
Morales M
影响因子：
3.7
作者：
Margolis EB;Toy B;Himmels P;Morales M;Fields HL
通讯作者：
Fields HL
影响因子：
3.7
作者：
Ntamati NR;Creed M;Achargui R;Lüscher C
通讯作者：
Lüscher C
影响因子：
16.2
作者：
Bromberg-Martin, Ethan S.;Matsumoto, Masayuki;Hikosaka, Okihide
通讯作者：
Hikosaka, Okihide
影响因子：
4.7
作者：
Dal Bo, G;St-Gelais, F;Trudeau, LE
通讯作者：
Trudeau, LE