Ventral Tegmental Area GABA, glutamate, and glutamate‐GABA neurons are heterogeneous in their electrophysiological and pharmacological properties

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Abstract

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 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.

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