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Research ArticleResearch Article: New Research, Cognition and Behavior

Lateral Orbitofrontal Cortex and Basolateral Amygdala Regulate Sensitivity to Delayed Punishment during Decision-Making

Anna E. Liley, Daniel B. K. Gabriel and Nicholas W. Simon
eNeuro 29 August 2022, 9 (5) ENEURO.0170-22.2022; DOI: https://doi.org/10.1523/ENEURO.0170-22.2022
Anna E. Liley
Department of Psychology, University of Memphis, Memphis, TN 38152
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Daniel B. K. Gabriel
Department of Psychology, University of Memphis, Memphis, TN 38152
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Nicholas W. Simon
Department of Psychology, University of Memphis, Memphis, TN 38152
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Article Figures & Data

Figures

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  • Figure 1.
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    Figure 1.

    a, Delayed punishment decision-making task (DPDT and REVDPDT). Rats chose between two levers, one delivering a one-pellet reward and the other delivering a three-pellet reward accompanied by a delayed foot shock (delay sequence: 0, 4, 8, 12, 16 s, No Shock/Delay for DPDT; No Shock/Delay, 16, 12, 8, 4, 0 s for REVDPDT). b, A six-day microinfusion schedule was used for both brain regions, with inactivation and saline order (days 3 and 5) counterbalanced across subjects.

  • Figure 2.
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    Figure 2.

    Histologic confirmation of cannulae placements in Lateral orbitofrontal cortex (a) and basolateral amygdala (b).

  • Figure 3.
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    Figure 3.

    a, Lateral orbitofrontal cortex (LOFC) inactivation reduced choice of rewards with delayed punishment without affecting choice of immediate or short-delay punishment. b, c, Females and males showed comparable reduction in choice of delayed but not immediate punishment after LOFC inactivation. All panels display data as mean ± standard error of the mean (SEM). See Extended Data Figure 3-1.

  • Figure 4.
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    Figure 4.

    a, Lateral orbitofrontal cortex (LOFC) inactivation increased free choice omissions compared with saline, and omissions were most prevalent when punishment occurred after shorter delays. b, c, Females displayed more free choice omissions throughout the task than males. d, LOFC infusions did not affect latency to choose either lever. e, f, Females took longer to choose the punished lever after LOFC inactivation than males. All panels display data as mean ± SEM. See Extended Data Figures 4-1 and 4-2.

  • Figure 5.
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    Figure 5.

    a, Inactivation of Lateral orbitofrontal cortex (LOFC) during REVDPDT shifted choice away from the punished reward as delays decreased. b, c, Females and males displayed similar reduction in choice of the punished lever compared with safe when delays decreased during LOFC inactivation. All panels display data as mean ± SEM. See Extended Data Figure 3-1.

  • Figure 6.
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    Figure 6.

    a, Inactivation of Lateral orbitofrontal cortex (LOFC) during REVDPDT increased free choice omissions during inactivation compared with saline. b, c, Females omitted more free choice trials than males throughout the task. d, There were no differences in latency to choose either the punished or safe levers for both inactivation and saline infusions during REVDPDT. e, f, Females required more time to select the punished lever than males. All panels display data as mean ± SEM. See Extended Data Figures 4-1 and 4-2.

  • Figure 7.
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    Figure 7.

    a, Basolateral amygdala (BLA) inactivation did not affect choice when punishment was immediate, but reduced choice of the punished reward when delays were longer. b, c, Females and males both displayed reduction in choice of delayed punishment but not immediate punishment following BLA inactivation. All panels display data as mean ± SEM. See Extended Data Figure 3-1.

  • Figure 8.
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    Figure 8.

    a, Subjects increased free choice omissions during longer delay times of DPDT following Basolateral amygdala (BLA) inactivation compared with saline. b, c, Females had more free choice omissions than males throughout the task. d, There were no effects of inactivation or saline on latency to choose between the punished and safe levers. e, f, Females required more time to choose a lever than males. All panels display data as mean ± SEM. See Extended Data Figures 4-1 and 4-2.

  • Figure 9.
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    Figure 9.

    a, Basolateral amygdala (BLA) inactivation did not affect decision-making during REVDPDT. b, c, Neither females nor males were affected by BLA inactivation. All panels display data as mean ± SEM. See Extended Data Figure 3-1.

  • Figure 10.
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    Figure 10.

    a, Basolateral amygdala (BLA) inactivation did not affect free choice omissions during REVDPDT. b, c, Females and males displayed a comparable number of free choice omissions. d, Latency to choose between the punished and safe levers was not affected by inactivation. e, f, Females had greater latency to select a lever than males. All panels display data as mean ± SEM. See Extended Data Figures 4-1 and 4-2.

Tables

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    Table 1

    t test results comparing average selection of the punished lever following inactivation versus saline during lateral orbitofrontal cortex (LOFC) DPDT (a) and t test results comparing average selection of the punished lever following inactivation versus saline during LOFC REVDPDT (b)

    LOFC
    aDelayMean differencestdfp
    0 s6.760.894110.39
         
    4 s0.560.083110.935
         
    8 s−3.75−0.516110.616
         
    12 s−23.43−1.971110.074
         
    16 s−36.67−3.552110.005*
         
    No Shock−21.67−1.516110.158
    bDelayMean differencestdfp
    No Shock−11.79−1.863130.085
         
    16 s−25.56−2.816130.015*
         
    12 s−16.39−1.34130.203
         
    8 s−9.75−0.821130.426
         
    4 s−7.08−0.582130.571
         
    0 s−3.36−0.392130.701
          
    • Mean difference represents saline mean - inactivation mean.

    • View popup
    Table 2

    t test results comparing average selection of the punished lever following inactivation versus saline during Basolateral amygdala (BLA) DPDT (a) and t test results comparing average selection of the punished lever following inactivation versus saline during BLA REVDPDT (b)

    BLA
    aDelayMean differencetdfp
    0 s−1.01−0.125130.902
         
    4 s12.071.247130.234
         
    8 s−9.23−0.775130.452
         
    12 s−10.05−0.863130.404
         
    16 s−23.81−2.787130.015*
         
    No Shock−19.29−3.006130.010*
    bDelayMean differencetdfp
    No Shock−7.33−0.929140.369
         
    16 s−7.09−1.245140.234
         
    12 s−9.46−1.049140.312
         
    8 s−1.09−0.113140.912
         
    4 s−3.23−0.285140.78
         
    0 s−3.28−0.382140.708
    • Both include mean differences between BLA inactivation and saline. Mean difference represents saline mean - inactivation mean.

Extended Data

  • Figures
  • Tables
  • Extended data Figure 3-1

    Statistics summarizing effects of LOFC and BLA inactivation on decision-making with immediate vs. delayed punishment. Data for these analyses are visualized in figures 3,5,7, and 9.

    [enu-eN-NWR-0170-22-s02.doc]
  • Extended data Figure 4-1

    Statistics summarizing effects of LOFC and BLA inactivation on trial omissions. Data for these analyses are visualized in figures 4,6,8, and 10.

    [enu-eN-NWR-0170-22-s03.doc]
  • Extended data Figure 4-2

    Statistics summarizing effects of LOFC and BLA inactivation on choice latency. Data for these analyses are visualized in figures 4,6,8, and 10.

    [enu-eN-NWR-0170-22-s04.doc]
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Lateral Orbitofrontal Cortex and Basolateral Amygdala Regulate Sensitivity to Delayed Punishment during Decision-Making
Anna E. Liley, Daniel B. K. Gabriel, Nicholas W. Simon
eNeuro 29 August 2022, 9 (5) ENEURO.0170-22.2022; DOI: 10.1523/ENEURO.0170-22.2022

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Lateral Orbitofrontal Cortex and Basolateral Amygdala Regulate Sensitivity to Delayed Punishment during Decision-Making
Anna E. Liley, Daniel B. K. Gabriel, Nicholas W. Simon
eNeuro 29 August 2022, 9 (5) ENEURO.0170-22.2022; DOI: 10.1523/ENEURO.0170-22.2022
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Keywords

  • basolateral amygdala
  • decision-making
  • delay discounting
  • lateral orbitofrontal cortex
  • punishment

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