Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making

Alexander Friedman, Daigo Homma, Bernard Bloem, Leif G. Gibb, Ken ichi Amemori, Dan Hu, Sebastien Delcasso, Timothy F. Truong, Joyce Yang, Adam S. Hood, Katrina A. Mikofalvy, Dirk W. Beck, Norah Nguyen, Erik D. Nelson, Sebastian E. Toro Arana, Ruth H. Vorder Bruegge, Ki A. Goosens, Ann M. Graybiel

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, “rational” decision-making. This capacity is vulnerable in neuropsychiatric disorders and in the aftermath of chronic stress, in which aberrant choices and high-risk behaviors occur. We report that chronic stress exposure in rodents produces abnormal evaluation of costs and benefits resembling non-optimal decision-making in which choices of high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond with increased activity of their striosome-predominant striatal projection neuron targets and with decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked or be mimicked by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict.

Original languageEnglish
Pages (from-to)1191.e28-1205.e28
Issue number5
StatePublished - 16 Nov 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.


The authors thank Henry Hall and Yasuo Kubota for their help in many aspects of this work and the undergraduate students who assisted with these experiments. This work was funded by the NIH/NIMH (R01 MH060379 ), the CHDI Foundation ( A-5552 ), the Defense Advanced Research Projects Agency and the U.S. Army Research Office ( W911NF-10-1-0059 ), the Bachmann-Strauss Dystonia & Parkinson Foundation , the William N. & Bernice E. Bumpus Foundation (RRDA Pilot: 2013.1 ), and the Saks Kavanaugh Foundation .

FundersFunder number
NIH/NIMHR01 MH060379
Saks Kavanaugh Foundation
U.S. Army Research OfficeW911NF-10-1-0059
William N. & Bernice E. Bumpus Foundation2013.1
National Institute of Mental HealthR01MH060379
Defense Advanced Research Projects Agency
Bachmann-Strauss Dystonia and Parkinson Foundation
CHDI FoundationA-5552
Japan Society for the Promotion of Science17H06771


    • basal ganglia
    • cost-benefit
    • excitation-inhibition balance
    • fast-spiking interneurons
    • optogenetics
    • parvalbumin-positive interneurons
    • prefrontal cortex
    • prelimbic cortex
    • striatum


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