Midbrain circuit regulation of individual alcohol drinking behaviors in mice

Barbara Juarez, Carole Morel, Stacy M. Ku, Yutong Liu, Hongxing Zhang, Sarah Montgomery, Hilledna Gregoire, Efrain Ribeiro, Marshall Crumiller, Ciorana Roman-Ortiz, Jessica J. Walsh, Kelcy Jackson, Denise E. Croote, Yingbo Zhu, Song Zhang, Leandro F. Vendruscolo, Scott Edward, Amanda Roberts, Georgia E. Hodes, Yongke LuErin S. Calipari, Dipesh Chaudhury, Allyson K. Friedman, Ming Hu Han

Research output: Contribution to journalArticle

Abstract

Alcohol-use disorder (AUD) is the most prevalent substance-use disorder worldwide. There is substantial individual variability in alcohol drinking behaviors in the population, the neural circuit mechanisms of which remain elusive. Utilizing in vivo electrophysiological techniques, we find that low alcohol drinking (LAD) mice have dramatically higher ventral tegmental area (VTA) dopamine neuron firing and burst activity. Unexpectedly, VTA dopamine neuron activity in high alcohol drinking (HAD) mice does not differ from alcohol naive mice. Optogenetically enhancing VTA dopamine neuron burst activity in HAD mice decreases alcohol drinking behaviors. Circuit-specific recordings reveal that spontaneous activity of nucleus accumbens-projecting VTA (VTA-NAc) neurons is selectively higher in LAD mice. Specifically activating this projection is sufficient to reduce alcohol consumption in HAD mice. Furthermore, we uncover ionic and cellular mechanisms that suggest unique neuroadaptations between the alcohol drinking groups. Together, these data identify a neural circuit responsible for individual alcohol drinking behaviors.

Original languageEnglish (US)
Article number2220
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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  • Cite this

    Juarez, B., Morel, C., Ku, S. M., Liu, Y., Zhang, H., Montgomery, S., Gregoire, H., Ribeiro, E., Crumiller, M., Roman-Ortiz, C., Walsh, J. J., Jackson, K., Croote, D. E., Zhu, Y., Zhang, S., Vendruscolo, L. F., Edward, S., Roberts, A., Hodes, G. E., ... Han, M. H. (2017). Midbrain circuit regulation of individual alcohol drinking behaviors in mice. Nature communications, 8(1), [2220]. https://doi.org/10.1038/s41467-017-02365-8