Modulation of ventromedial orbitofrontal cortical glutamatergic activity affects the explore-exploit balance and influences value-based decision-making

Author:

Barnes Samuel A12,Dillon Daniel G34,Young Jared W12,Thomas Michael L15,Faget Lauren6,Yoo Ji Hoon6,Der-Avakian Andre1,Hnasko Thomas S67,Geyer Mark A12,Ramanathan Dhakshin S128ORCID

Affiliation:

1. Department of Psychiatry, University of California San Diego , 9500 Gilman Dr,  La Jolla, CA 92093, United States

2. Department of Mental Health, VA San Diego Healthcare System , 3350 La Jolla Village Dr, La Jolla, CA 92093 , United States

3. Center for Depression, Anxiety and Stress Research, McLean Hospital , 115 Mill St,  Belmont, MA 02478, United States

4. Department of Psychiatry, Harvard Medical School , 401 Park Drive, Boston, MA 02115 , United States

5. Colorado State University Department of Psychology, 1876 Campus Delivery,  , Fort Collins, CO 80523 , United States

6. Department of Neurosciences, University of California San Diego , 9500 Gilman Dr, La Jolla, CA 92093 , United States

7. Research Service, VA San Diego Healthcare System , San Diego, CA, 92161 , United States

8. Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System , 3350 La Jolla Village Dr, La Jolla, CA 92093 , United States

Abstract

Abstract The balance between exploration and exploitation is essential for decision-making. The present study investigated the role of ventromedial orbitofrontal cortex (vmOFC) glutamate neurons in mediating value-based decision-making by first using optogenetics to manipulate vmOFC glutamate activity in rats during a probabilistic reversal learning (PRL) task. Rats that received vmOFC activation during informative feedback completed fewer reversals and exhibited reduced reward sensitivity relative to rats. Analysis with a Q-learning computational model revealed that increased vmOFC activity did not affect the learning rate but instead promoted maladaptive exploration. By contrast, vmOFC inhibition increased the number of completed reversals and increased exploitative behavior. In a separate group of animals, calcium activity of vmOFC glutamate neurons was recorded using fiber photometry. Complementing our results above, we found that suppression of vmOFC activity during the latter part of rewarded trials was associated with improved PRL performance, greater win-stay responding and selecting the correct choice on the next trial. These data demonstrate that excessive vmOFC activity during reward feedback disrupted value-based decision-making by increasing the maladaptive exploration of lower-valued options. Our findings support the premise that pharmacological interventions that normalize aberrant vmOFC glutamate activity during reward feedback processing may attenuate deficits in value-based decision-making.

Funder

Burroughs-Wellcome Fund Career Award for Medical Scientists

VA Career Development Award

NARSAD Young Investigator

National Institute of Mental Health

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Cognitive Neuroscience

Reference76 articles.

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