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The nucleus accumbens and ventral pallidum exhibit greater dopaminergic innervation in humans compared to other primates

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Abstract

Recent evidence suggests that increased dopaminergic signaling within the dorsal striatum played a central role in the evolution of the human brain. This increase has been linked to human prosociality and language in what has been described as a dopamine-dominated striatum personality style. Increased striatal dopamine is associated with an increase in ventral striatal activity and promotes externally driven behaviors, including cooperation and social conformity. In contrast, decreased striatal dopamine is associated with increased dorsal striatal activity and favors internally driven and goal-oriented behaviors. Previous comparative studies have focused on the dorsal striatum, measuring dopaminergic innervation in the dorsal and medial caudate nucleus and putamen. Here, we add to this knowledge by examining regions of the ventral striatum. We quantified the density of tyrosine hydroxylase–immunoreactive axons, as a measure of dopaminergic innervation, in the nucleus accumbens and ventral pallidum of humans, great apes, platyrrhine and cercopithecid monkeys. Our data show that humans have a significantly greater dopaminergic innervation in both structures, supporting the hypothesis that selection for a prosocial neurochemistry in the human basal ganglia may have contributed to the evolution of our uniquely social behavior profile.

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Availability of data and materials

All raw data are available and will be posted in the National Chimpanzee Brain Resource website data repository (https://www.chimpanzeebrain.org/data-repository) and can be requested from the corresponding authors.

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Acknowledgements

This research was funded by the National Science Foundation (NSF BCS-1846201 to MAR and SMA-1542848 and EF-2021785 to CCS and WDH). Elaine Miller was supported by the National Science Foundation Graduate Research Fellowship Program (1746914). We would like to thank Dr. Richard S. Meindl for statistical advice. We are grateful to each of the following for the use of brain materials: The NIH NeuroBioBank, National Chimpanzee Brain Resource (NIH grant NS092988), NINDS Grants NS-402867 and NS0-73134, The Great Ape Aging Project (supported by NIH Grant AG014308), the National Primate Research Center at the University of Washington (NIH grant RR000166), the Oregon National Primate Research Center (NIH P51 OD011092), the Northwestern University Alzheimer’s Disease Center Brain Bank (supported by Alzheimer’s Disease Core Center Grant AG013854, from the National Institute on Aging to Northwestern University, Chicago, IL).

Funding

This research was funded by the National Science Foundation (NSF BCS-1846201 to MAR and SMA-1542848 and EF-2021785 to CCS and WDH). Elaine Miller was supported by the National Science Foundation Graduate Research Fellowship Program (1746914).

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Authors and Affiliations

  1. Department of Anthropology and School of Biomedical Sciences, Kent State University, Kent, OH, USA

    Kristen N. Hirter, C. Owen Lovejoy & Mary Ann Raghanti

  2. Brain Health Research Institute, Kent State University, Kent, OH, USA

    Kristen N. Hirter, C. Owen Lovejoy & Mary Ann Raghanti

  3. Department of Anthropology and Center for the Advanced Study of Human Paleobiology, The George Washington University, Washington, DC, USA

    Elaine N. Miller, Cheryl D. Stimpson & Chet C. Sherwood

  4. Department of Psychology, Trinity University, San Antonio, TX, USA

    Kimberley A. Phillips

  5. Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA

    Kimberley A. Phillips

  6. Department of Comparative Medicine, University of Texas MD Anderson Cancer Center, Bastrop, TX, USA

    William D. Hopkins

  7. Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Patrick R. Hof

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  1. Kristen N. Hirter
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Contributions

KH and MAR contributed to the study conception and design. Material preparation, data collection and analysis were performed by KH, EM, CDS, KAP, WDH, PRH, CCS, COL, and MAR. The first draft of the manuscript was written by KH and MAR and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Kristen N. Hirter or Mary Ann Raghanti.

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Human postmortem brain samples meet the criteria for IRB Exemption 4 under DHHS regulations 45 CFR 46 (46.101). Because no living subjects are involved in this research, this proposal does not qualify for IACUC oversight. However, when alive, all nonhuman primates were housed at research or zoological institutions and were maintained in accordance with each institution’s animal care and use guidelines.

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Hirter, K.N., Miller, E.N., Stimpson, C.D. et al. The nucleus accumbens and ventral pallidum exhibit greater dopaminergic innervation in humans compared to other primates. Brain Struct Funct 226, 1909–1923 (2021). https://doi.org/10.1007/s00429-021-02300-0

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  • DOI: https://doi.org/10.1007/s00429-021-02300-0

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