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      Relative Contributions and Mapping of Ventral Tegmental Area Dopamine and GABA Neurons by Projection Target in the Rat

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          Abstract

          The ventral tegmental area (VTA) is a heterogeneous midbrain structure that contains dopamine (DA), GABA, and glutamate neurons that project to many different brain regions. Here, we combined retrograde tracing with immunocytochemistry against tyrosine hydroxylase (TH) or glutamate decarboxylase (GAD) to systematically compare the proportion of dopaminergic and GABAergic VTA projections to 10 target nuclei: anterior cingulate, prelimbic, and infralimbic cortex; nucleus accumbens core, medial shell, and lateral shell; anterior and posterior basolateral amygdala; ventral pallidum; and periaqueductal gray. Overall, the non-dopaminergic component predominated VTA efferents, accounting for more than 50% of all projecting neurons to each region except the nucleus accumbens core. In addition, GABA neurons contributed no more than 20% to each projection, with the exception of the projection to the ventrolateral periaqueductal gray, where the GABAergic contribution approached 50%. Therefore, there is likely a significant glutamatergic component to many of the VTA's projections. We also found that VTA cell bodies retrogradely labeled from the various target brain regions had distinct distribution patterns within the VTA, including in the locations of DA and GABA neurons. Despite this patterned organization, VTA neurons comprising these different projections were intermingled and never limited to any one subregion. These anatomical results are consistent with the idea that VTA neurons participate in multiple distinct, parallel circuits that differentially contribute to motivation and reward. While attention has largely focused on VTA DA neurons, a better understanding of VTA subpopulations, especially the contribution of non-DA neurons to projections, will be critical for future work.

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          Author and article information

          Journal
          Journal of Comparative Neurology
          J Comp Neurol
          Wiley
          00219967
          November 04 2018
          Affiliations
          [1 ]Helen Wills Neuroscience Institute; University of California, Berkeley; Berkeley, California 94720
          [2 ]Department of Neurology and Wheeler Center for the Neurobiology of Addiction; University of California; San Francisco, California 94143
          [3 ]Ernest Gallo Clinic and Research Center; University of California; San Francisco, Emeryville, California 94608
          Article
          10.1002/cne.24572
          6347508
          30393861
          1008378f-8b3e-4ed9-9737-b6824fb9a03e
          © 2018

          http://doi.wiley.com/10.1002/tdm_license_1.1

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