Projection-Target-Defined Effects of Orexin and Dynorphin on VTA Dopamine Neurons

Cell Rep. 2017 Feb 7;18(6):1346-1355. doi: 10.1016/j.celrep.2017.01.030.


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.

Keywords: dopamine; dynorphin; orexin; ventral tegmental area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism*
  • Dynorphins / metabolism*
  • Female
  • Hypothalamus / metabolism
  • Male
  • Mice
  • Neural Pathways / metabolism
  • Neuropeptides / metabolism
  • Nucleus Accumbens / metabolism
  • Orexins / metabolism*
  • Reward
  • Ventral Tegmental Area / metabolism*


  • Neuropeptides
  • Orexins
  • Dynorphins
  • Dopamine