Nucleus Accumbens Subnuclei Regulate Motivated Behavior via Direct Inhibition and Disinhibition of VTA Dopamine Subpopulations

Neuron. 2018 Jan 17;97(2):434-449.e4. doi: 10.1016/j.neuron.2017.12.022. Epub 2018 Jan 4.


Mesolimbic dopamine (DA) neurons play a central role in motivation and reward processing. Although the activity of these mesolimbic DA neurons is controlled by afferent inputs, little is known about the circuits in which they are embedded. Using retrograde tracing, electrophysiology, optogenetics, and behavioral assays, we identify principles of afferent-specific control in the mesolimbic DA system. Neurons in the medial shell subdivision of the nucleus accumbens (NAc) exert direct inhibitory control over two separate populations of mesolimbic DA neurons by activating different GABA receptor subtypes. In contrast, NAc lateral shell neurons mainly synapse onto ventral tegmental area (VTA) GABA neurons, resulting in disinhibition of DA neurons that project back to the NAc lateral shell. Lastly, we establish a critical role for NAc subregion-specific input to the VTA underlying motivated behavior. Collectively, our results suggest a distinction in the incorporation of inhibitory inputs between different subtypes of mesolimbic DA neurons.

Keywords: GABA; dopamine; mesolimbic; motivation; nucleus accumbens; reward; ventral tegmental area.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / physiology
  • Animals
  • Behavior, Animal / physiology*
  • Channelrhodopsins / physiology
  • Channelrhodopsins / radiation effects
  • Conditioning, Operant
  • Dopamine / physiology
  • Dopaminergic Neurons / classification
  • Dopaminergic Neurons / physiology*
  • Exploratory Behavior
  • Female
  • GABAergic Neurons / physiology
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Motivation
  • Nucleus Accumbens / physiology*
  • Optogenetics
  • Reward
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / physiology*


  • Channelrhodopsins
  • Dopamine