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

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

Author information

1
Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, 142 Life Science Addition #3200, CA 94720, USA.
2
Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, 142 Life Science Addition #3200, CA 94720, USA. Electronic address: lammel@berkeley.edu.

Abstract

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

PMID:
29307710
PMCID:
PMC5773387
[Available on 2019-01-17]
DOI:
10.1016/j.neuron.2017.12.022

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