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

• DOI: 10.1016/j.celrep.2017.01.030
• Publication Date: 2017-02-07T19:34:59Z
• Authors: Corey Baimel; Benjamin K. Lau; Min Qiao; Stephanie L. Borg...
• Keywords: Male; 0301 basic medicine; Orexins; QH301-705.5; Dopamine; Dopaminergic Neurons; Neuropeptides; Ventral Tegmental Area; ventral tegmental area; Hypothalamus; Dynorphins; Nucleus Accumbens; Mice; 03 medical and health sciences; orexin; Reward; Neural Pathways; Animals; Female; dopamine; Biology (General); dynorphin

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.