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

Publication date: 7 February 2017
Source:Cell Reports, Volume 18, Issue 6
Author(s): Corey Baimel, Benjamin K. Lau, Min Qiao, Stephanie L. Borgland
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.

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Teaser

Baimel et al. find that the projection target is an important determinant of neuromodulation by the lateral hypothalamic orexin and dynorphin input. Moreover, both the anatomical distribution and the intrinsic properties of VTA dopamine neurons are also defined by projection target.


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