Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

Featured Paper of the Month – August 2021

Published in European Journal of Neuroscience by Jorge Miranda-Barrientos and Marisela Morales, et al. in the NIDA IRP Neuronal Networks Section.

Summary

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. SIGNIFICANT STATEMENT: Some physiological properties of VTA glutamate-releasing and glutamate-GABA co-releasing neurons are distinct from those of VTA GABA-releasing neurons. µ-opioid receptor activation hyperpolarizes some VTA glutamate-releasing and some GABA-releasing neurons.

Publication Information

Miranda-Barrientos, Jorge; Chambers, Ian; Mongia, Smriti; Liu, Bing; Wang, Hui-Ling; Mateo-Semidey, Gabriel E; Margolis, Elyssa B; Zhang, Shiliang; Morales, Marisela

Ventral tegmental area GABA, glutamate, and glutamate-GABA neurons are heterogeneous in their electrophysiological and pharmacological properties Journal Article

In: European Journal of Neuroscience, vol. 54, no. 1, pp. 4061-4084, 2021.

Abstract | Links

@article{https://doi.org/10.1111/ejn.15156,

title = {Ventral tegmental area GABA, glutamate, and glutamate-GABA neurons are heterogeneous in their electrophysiological and pharmacological properties},

author = {Jorge Miranda-Barrientos and Ian Chambers and Smriti Mongia and Bing Liu and Hui-Ling Wang and Gabriel E Mateo-Semidey and Elyssa B Margolis and Shiliang Zhang and Marisela Morales},

url = {https://pubmed.ncbi.nlm.nih.gov/33619763/},

doi = {https://doi.org/10.1111/ejn.15156},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {European Journal of Neuroscience},

volume = {54},

number = {1},

pages = {4061-4084},

abstract = {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 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. Significant statement Some physiological properties of VTA glutamate-releasing and glutamate-GABA co-releasing neurons are distinct from those of VTA GABA-releasing neurons. µ-opioid receptor activation hyperpolarizes some VTA glutamate-releasing and some GABA-releasing neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}