Neuron
Volume 101, Issue 1, 2 January 2019, Pages 133-151.e7
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Article
A Neural Circuit Mechanism for Encoding Aversive Stimuli in the Mesolimbic Dopamine System

https://doi.org/10.1016/j.neuron.2018.11.005Get rights and content
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Highlights

  • DA terminals in ventral NAc medial shell (vNAcMed) are excited by aversive stimuli

  • DA terminals in all other NAc subregions are inhibited by aversive stimuli

  • Excitation to reward-predictive cues is absent in vNAcMed DA terminals

  • DA→vNAcMed neurons encode aversive-predicting stimuli through LH-VGLUT2 inputs

Summary

Ventral tegmental area (VTA) dopamine (DA) neurons play a central role in mediating motivated behaviors, but the circuitry through which they signal positive and negative motivational stimuli is incompletely understood. Using in vivo fiber photometry, we simultaneously recorded activity in DA terminals in different nucleus accumbens (NAc) subnuclei during an aversive and reward conditioning task. We find that DA terminals in the ventral NAc medial shell (vNAcMed) are excited by unexpected aversive outcomes and to cues that predict them, whereas DA terminals in other NAc subregions are persistently depressed. Excitation to reward-predictive cues dominated in the NAc lateral shell and was largely absent in the vNAcMed. Moreover, we demonstrate that glutamatergic (VGLUT2-expressing) neurons in the lateral hypothalamus represent a key afferent input for providing information about aversive outcomes to vNAcMed-projecting DA neurons. Collectively, we reveal the distinct functional contributions of separate mesolimbic DA subsystems and their afferent pathways underlying motivated behaviors.

Keywords

dopamine
ventral tegmental area
nucleus accumbens
aversion
reward
lateral hypothalamus
dorsal raphe

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These authors contributed equally

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