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Research ArticleResearch Article: New Research, Disorders of the Nervous System

The Ventral Pallidum Innervates a Distinct Subset of Midbrain Dopamine Neurons

Olivia J. Yang, Hannah B. Elam, Kayla Lilly, Alexandra M. McCoy, Valeriia Klepikova, Stephanie M. Perez and Daniel J. Lodge
eNeuro 7 October 2025, 12 (10) ENEURO.0222-25.2025; https://doi.org/10.1523/ENEURO.0222-25.2025
Olivia J. Yang
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229
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  • ORCID record for Olivia J. Yang
Hannah B. Elam
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229
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Kayla Lilly
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229
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Alexandra M. McCoy
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229
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Valeriia Klepikova
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229
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Stephanie M. Perez
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229
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Daniel J. Lodge
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229
2South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Texas 78229
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  • Figure 1.
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    Figure 1.

    Schematic depicting afferent inputs to VP that modulate VTA dopamine neuron population activity and the role of these inputs in various pathological states. Ventral hippocampus (vHipp); paraventricular nucleus of the thalamus (PVT); nucleus accumbens (NAc); basolateral amygdala (BLA); ventral pallidum (VP); ventral tegmental area (VTA); major depressive disorder (MDD).

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    Figure 2.

    The proportion of VTA dopamine neurons inhibited by VP stimulation increases after vHipp activation. A, The proportion of VTA dopamine neurons unaffected, activated, or inhibited by VP stimulation after delivery of vehicle or NMDA into the vHipp. B, The number of spontaneously active VTA dopamine neurons (population activity) after delivery of vehicle or NMDA into the vHipp. C, The percentage of action potentials firing in bursts. D, Firing frequency of recorded dopamine neurons at the baseline and during VP stimulation. E, F, Average firing frequency (E) or percentage action potentials firing in bursts (F) of dopamine neurons unaffected, excited, or inhibited by VP stimulation. G, H, Representative brain slices of (G) VP (gray square) with stimulating electrode placement (arrow), (H) vHipp (open square) with cannula placement (open arrow), and VTA (gray square) with recording electrode placement (black arrow). I, Representative peristimulus time histograms for dopamine neurons unaffected, excited, or inhibited by VP stimulation. J, Representative electrophysiology recording of dopamine neurons before and during VP stimulations (black bar) and action potential traces for dopamine neuron unaffected, excited, or inhibited by VP stimulation. ***p < 0.001.

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    Figure 3.

    The VP projects to a subset of VTA dopamine neurons. A, Schematic depicting monosynaptic labeling using H129 and helper virus and injection timeline. B, Representative brain slice of VP with cannula placement (arrow). C, Representative brain slice of mesencephalon containing VTA and tyrosine hydroxylase (TH) immunolabeling (green). D, Representative images of cells in VTA indicating colocalized cells (left, white circles), TH+ only cells (middle, green circles), and tdTomato (Td)+ only cells (right, red circles). E, The percentage of TH+ cells colabeled with Td (left) and the percentage of Td+ cells colabeled with TH (right). F, The number of colocalized cells along the medial (M)/lateral (L) axis. G, The number of colocalized cells along the anterior (A)/posterior (P) axis.

Tables

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    Table 1.

    Statistical table indicating data structure and confidence intervals for all statistical analysis

    FigureData structureType of testPower
    aFigure 2AContingency tableχ2N/A
    bFigure 2BNormal distributiont test95% CI [0.31,0.88]
    cFigure 2CNot normally distributedMann–Whitney95% CI [−5.0,6.2]
    dFigure 2DNot normally distributedART ANOVA

    95% CI

    Veh [188,221]

    NMDA [194,227]

    BL [198,231]

    Stim [184,217]

    eFigure 2ENot normally distributedKruskal–Wallis95% CI [2.98,3.72; 2.27,4.19; 3.41,4.23]
    fFigure 2FNot normally distributedKruskal–Wallis95% CI [20.92,30.05; 26.78,50.17; 25.25,37.75]
    gFigure 3ENormal distributiont test95% CI [−21.6 to 16.6]
    hFigure 3FNormal distributionOne-way ANOVA95% CI [20.64,50.27; 23.81,57.08; 19.66,64.76]
    iFigure 3GNormal distributionOne-way ANOVA95% CI [34.32,171.7; 105.4,210.6; 74.08,258.9; −0.4113,149.1]
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The Ventral Pallidum Innervates a Distinct Subset of Midbrain Dopamine Neurons
Olivia J. Yang, Hannah B. Elam, Kayla Lilly, Alexandra M. McCoy, Valeriia Klepikova, Stephanie M. Perez, Daniel J. Lodge
eNeuro 7 October 2025, 12 (10) ENEURO.0222-25.2025; DOI: 10.1523/ENEURO.0222-25.2025

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The Ventral Pallidum Innervates a Distinct Subset of Midbrain Dopamine Neurons
Olivia J. Yang, Hannah B. Elam, Kayla Lilly, Alexandra M. McCoy, Valeriia Klepikova, Stephanie M. Perez, Daniel J. Lodge
eNeuro 7 October 2025, 12 (10) ENEURO.0222-25.2025; DOI: 10.1523/ENEURO.0222-25.2025
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Keywords

  • dopamine
  • psychiatric disorders
  • schizophrenia
  • ventral pallidum

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