Projection-Target-Defined Effects of Orexin and Dynorphin on VTA Dopamine Neurons.
Circuit-specific signaling of ventral tegmental area (VTA) dopamine neurons drives different aspects of motivated behavior, but the neuromodulatory control of these circuits is unclear. We tested the actions of co-expressed lateral hypothalamic peptides, orexin A (oxA) and dynorphin (dyn), on projection-target-defined dopamine neurons in mice. We determined that VTA dopamine neurons that project to the nucleus accumbens lateral shell (lAcbSh), medial shell (mAcbSh), and basolateral amygdala (BLA) are largely non-overlapping cell populations with different electrophysiological properties. Moreover, the neuromodulatory effects of oxA and dyn on these three projections differed. OxA selectively increased firing in lAcbSh- and mAcbSh-projecting dopamine neurons. Dyn decreased firing in the majority of mAcbSh- and BLA-projecting dopamine neurons but reduced firing only in a small fraction of those that project to the lAcbSh. In conclusion, the oxA-dyn input to the VTA may drive reward-seeking behavior by tuning dopaminergic output in a projection-target-dependent manner.
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
Corey
C
Baimel
Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
Benjamin K
BK
Lau
Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
Min
M
Qiao
Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada. Electronic address: s.borgland@ucalgary.ca.
Stephanie L
SL
Borgland
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004399:Dynorphins / Q000378:metabolism*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D009434:Neural Pathways / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism*; D012201:Reward; D017557:Ventral Tegmental Area / Q000378:metabolism*
D009479:Neuropeptides; D000068797:Orexins; D004399:Dynorphins; D004298:Dopamine
dopamine; dynorphin; orexin; ventral tegmental area