TY - JOUR
T1 - Midbrain circuit regulation of individual alcohol drinking behaviors in mice
AU - Juarez, Barbara
AU - Morel, Carole
AU - Ku, Stacy M.
AU - Liu, Yutong
AU - Zhang, Hongxing
AU - Montgomery, Sarah
AU - Gregoire, Hilledna
AU - Ribeiro, Efrain
AU - Crumiller, Marshall
AU - Roman-Ortiz, Ciorana
AU - Walsh, Jessica J.
AU - Jackson, Kelcy
AU - Croote, Denise E.
AU - Zhu, Yingbo
AU - Zhang, Song
AU - Vendruscolo, Leandro F.
AU - Edward, Scott
AU - Roberts, Amanda
AU - Hodes, Georgia E.
AU - Lu, Yongke
AU - Calipari, Erin S.
AU - Chaudhury, Dipesh
AU - Friedman, Allyson K.
AU - Han, Ming Hu
N1 - Funding Information:
We thank G. F. Koob for his contribution on initial project design and continuing consultations; E. J. Nestler, S. J. Russo, R. C. Bagot, and E. A. Mouzon for their helpful discussions. We thank A. I. Cederbaum for his consultation on blood EtOH measurements. We would also like to thank the members of Icahn School of Medicine’s Center for Comparative Medicine and Surgery for their efforts in maintaining our animals. This work was supported by National Institute of Health grants: AA022445 to M.-H.H.; T32 MH087004 and F31 AA022862 to B.J.; T32MH096678 and F31 MH108326 to S.M.K.; F32 MH096464 to A.K.F. This work was also supported by NARSAD Independent Investigator Award to M.-H.H. and the National Science Foundation in China award (NSFC-81200862) to H.Z.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-02365-8
DO - 10.1038/s41467-017-02365-8
M3 - Article
C2 - 29263389
AN - SCOPUS:85038857594
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2220
ER -