Input-specific control of reward and aversion in the ventral tegmental area.
Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures, and whether inputs to the VTA differentially modulate such circuits. Here we show that, because of differences in synaptic connectivity, activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (γ-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours.
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA.
Stephan
S
Lammel
Byung Kook
BK
Lim
Chen
C
Ran
Kee Wui
KW
Huang
Michael J
MJ
Betley
Kay M
KM
Tye
Karl
K
Deisseroth
Robert C
RC
Malenka
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism; D019262:Habenula / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009434:Neural Pathways / Q000502:physiology*; D011954:Receptors, Dopamine / Q000378:metabolism; D012201:Reward; D013569:Synapses / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology / Q000502:physiology*
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D004298:Dopamine