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Chemogenetic Activation of Mesoaccumbal Gamma-Aminobutyric Acid Projections Selectively Tunes Responses to Predictive Cues When Reward Value Is Abruptly Decreased

  • Author Footnotes
    1 KTW and MF contributed equally to this work.
    Ken T. Wakabayashi
    Footnotes
    1 KTW and MF contributed equally to this work.
    Affiliations
    Department of Psychology, University of Nebraska–Lincoln, Lincoln, Nebraska
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  • Author Footnotes
    1 KTW and MF contributed equally to this work.
    Malte Feja
    Footnotes
    1 KTW and MF contributed equally to this work.
    Affiliations
    Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York
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  • Martin P.K. Leigh
    Affiliations
    Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York
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  • Ajay N. Baindur
    Affiliations
    Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York
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  • Mauricio Suarez
    Affiliations
    Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York

    Clinical Research Institute on Addictions, State University of New York at Buffalo, Buffalo, New York
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  • Paul J. Meyer
    Affiliations
    Department of Psychology, State University of New York at Buffalo, Buffalo, New York
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  • Caroline E. Bass
    Correspondence
    Address correspondence to Caroline E. Bass, Ph.D.
    Affiliations
    Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York

    Clinical Research Institute on Addictions, State University of New York at Buffalo, Buffalo, New York
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  • Author Footnotes
    1 KTW and MF contributed equally to this work.

      Abstract

      Background

      Mesolimbic circuits regulate the attribution of motivational significance to incentive cues that predict reward, yet this network also plays a key role in adapting reward-seeking behavior when the contingencies linked to a cue unexpectedly change. Here, we asked whether mesoaccumbal GABA (gamma-aminobutyric acid) projections enhance adaptive responding to incentive cues of abruptly altered reward value, and whether these effects were distinct from global activation of all ventral tegmental area GABA circuits.

      Methods

      We used a viral targeting system to chemogenetically activate mesoaccumbal GABA projections in male rats during a novel cue-dependent operant value-shifting task, in which the volume of a sucrose reward associated with a predictive cue is suddenly altered, from the beginning and throughout the session. We compared the results with global activation of ventral tegmental area GABA neurons, which will activate local inhibitory circuits and long loop projections.

      Results

      We found that activation of mesoaccumbal GABA projections decreases responding to incentive cues associated with smaller-than-expected rewards. This tuning of behavioral responses was specific to cues associated with smaller-than-expected rewards but did not impact measures related to consuming the reward. In marked contrast, activating all ventral tegmental area GABA neurons resulted in a uniform decrease in responding to incentive cues irrespective of changes in the size of the reward.

      Conclusions

      Targeted activation of mesoaccumbal GABA neurons facilitates adaptation in reward-seeking behaviors. This suggests that these projections may play a very specific role in associative learning processes.

      Keywords

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      Linked Article

      • The Ventral Tegmental Area to Accumbens GABAergic Projection: Promoting Prediction or Engineering Extinction?
        Biological PsychiatryVol. 89Issue 4
        • Preview
          The nucleus accumbens (NAc) is critical for setting the vigor of reward-seeking behavior and for learning to respond to reward-predictive cues. Aberrant NAc neuronal activity also contributes to neuropsychiatric diseases, such as drug and gambling addiction. Each of these processes depends critically on the projections to the NAc from the midbrain ventral tegmental area (VTA). Most studies of the VTA have focused on its dopamine neurons, which project mainly to the NAc and prefrontal cortex. Dopamine neurons both facilitate reward seeking and play a critical role in learning.
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