Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.22.216093v1?rss=1 Authors: Miranda-Barrientos, J. A., Chambers, I., Mongia, S., Liu, B., Wang, H.-L., Mateo-Semidey, G. E., Margolis, E. B., Zhang, S., Morales, M. Abstract: The ventral tegmental area (VTA) contains dopamine neurons intermixed with GABA-releasing (expressing vesicular GABA transporter, VGaT), glutamate-releasing (expressing vesicular glutamate transporter, VGluT2), and co-releasing (co-expressing VGaT and VGluT2) neurons. By delivering INTRSECT viral vectors into 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 voltage, 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 Mu opioid receptors, MOR) in VGluT2+ VGaT- and VGluT2- VGaT+ neurons, and their hyperpolarization by the MOR agonist DAMGO. Collectively, we demonstrate the utility of the double transgenic mouse to access VTA glutamate, glutamate-GABA and GABA neurons, and show some electrophysiological heterogeneity among them. Copy rights belong to original authors. Visit the link for more info