Imperial College London

Prof. William Wisden F. Med. Sci.

Faculty of Natural SciencesDepartment of Life Sciences

Chair in Molecular Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 9744w.wisden Website CV

 
 
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Location

 

401BSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Yu:2019:10.1101/684142,
author = {Yu, X and Ba, W and Zhao, G and Ma, Y and Harding, E and Yin, L and Wang, D and Shi, Y and Vyssotski, A and Dong, H and Franks, N and Wisden, W},
doi = {10.1101/684142},
journal = {bioRxiv.org},
title = {Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior},
url = {http://dx.doi.org/10.1101/684142},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Abstract The ventral tegmental area (VTA), an important source of dopamine, regulates goal- and reward-directed and social behaviors, wakefulness and sleep. Hyperactivation of dopamine neurons generates behavioral pathologies. But any roles of non-dopamine VTA neurons in psychiatric illness have been little explored. Lesioning or chemogenetically inhibiting VTA GABAergic (VTA Vgat ) neurons generated persistent wakefulness with mania-like qualities: locomotor activity was increased; sensitivity to D-amphetamine was heightened; immobility times decreased on the tail suspension and forced swim tests; and sucrose preference increased. Furthermore, after sleep deprivation, mice with lesioned VTA Vgat neurons did not catch up on the lost NREM sleep, even though they were starting from an already highly sleep-deprived baseline, suggesting that the sleep homeostasis process was bypassed. The mania-like behaviors, including the sleep loss, were reversed by the mood-stabilizing drug valproate, and re-emerged when valproate treatment was stopped. Lithium salts, however, had no effect. The mania like-behaviors partially depended on dopamine, because giving D1/D2/D3 receptor antagonists partially restored the behaviors, but also on VTA Vgat projections to the lateral hypothalamus (LH). Optically or chemogenetically inhibiting VTA Vgat terminals in the LH elevated locomotion and decreased immobility time during the tail suspension and forced swimming tests. VTA Vgat neurons are centrally positioned to help set an animal’s (and human’s) level of mental and physical activity. Inputs that inhibit VTA Vgat neurons intensify wakefulness (increased activity, enhanced alertness and motivation), qualities useful for acute survival. Taken to the extreme, however, decreased or failed inhibition from VTA Vgat neurons produces mania-like qualities (hyperactivity, hedonia, decreased sleep).
AU - Yu,X
AU - Ba,W
AU - Zhao,G
AU - Ma,Y
AU - Harding,E
AU - Yin,L
AU - Wang,D
AU - Shi,Y
AU - Vyssotski,A
AU - Dong,H
AU - Franks,N
AU - Wisden,W
DO - 10.1101/684142
PY - 2019///
TI - Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior
T2 - bioRxiv.org
UR - http://dx.doi.org/10.1101/684142
ER -