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Research ArticleResearch Article: New Research, Cognition and Behavior

Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model

Caitlin A. Orsini, Wonn S. Pyon, Richard J. Dragone, Mojdeh Faraji, Alexa-Rae Wheeler, Marjory Pompilus, Marcelo Febo, Jennifer L. Bizon and Barry Setlow
eNeuro 3 January 2023, 10 (1) ENEURO.0385-22.2022; https://doi.org/10.1523/ENEURO.0385-22.2022
Caitlin A. Orsini
1Department of Psychiatry, University of Florida, Gainesville, Florida 32610
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Wonn S. Pyon
2Department of Neuroscience, University of Florida, Gainesville, Florida 32610
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Richard J. Dragone
1Department of Psychiatry, University of Florida, Gainesville, Florida 32610
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Mojdeh Faraji
1Department of Psychiatry, University of Florida, Gainesville, Florida 32610
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Alexa-Rae Wheeler
2Department of Neuroscience, University of Florida, Gainesville, Florida 32610
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Marjory Pompilus
1Department of Psychiatry, University of Florida, Gainesville, Florida 32610
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Marcelo Febo
1Department of Psychiatry, University of Florida, Gainesville, Florida 32610
3McKnight Brain Institute, University of Florida, Gainesville, Florida 32610
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Jennifer L. Bizon
2Department of Neuroscience, University of Florida, Gainesville, Florida 32610
3McKnight Brain Institute, University of Florida, Gainesville, Florida 32610
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Barry Setlow
1Department of Psychiatry, University of Florida, Gainesville, Florida 32610
3McKnight Brain Institute, University of Florida, Gainesville, Florida 32610
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  • Figure 1.
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    Figure 1.

    Schematic of the risky decision making task. Each 40 s trial is initiated with the illumination of the house and food trough lights. A rat must nosepoke into the food trough to trigger the extension of one lever (forced-choice trials) or both levers (free-choice trials). A press on the small, safe lever yields 1 food pellet, delivered immediately. A press on the large, risky lever yields 2 food pellets, also delivered immediately, but accompanied by a varying probability of footshock delivery (0, 25, 50, 75, and 100%). After an intertrial interval ranging from 10 to 35 s (depending on how quickly the rat progresses through the trial components), a new trial begins.

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    Figure 2.

    Performance on the Risky Decision-making Task in young and aged rats. A, Aged rats made significantly fewer presses on the large, risky lever than young rats. B, Aged and young rats displayed comparable win–stay and lose–shift behavior in the RDT. C, Relative to latencies to press the small, safe lever, latencies to press the large, risky lever increased as the risk of punishment increased in young rats. D, Relative to latencies to press the small, safe lever, latencies to press the large, risky lever increased as the risk of punishment increased in aged rats. Data are represented as the mean (±SEM) number of large lever presses (A), the proportion of trials (B), or the latencies in seconds (C, D). *p ≤ 0.05.

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    Figure 3.

    Performance on a shock reactivity threshold assay in young and aged rats. Shock thresholds were not significantly different between young and aged rats. Data are represented as the mean (±SEM) shock reactivity threshold (in μA).

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    Figure 4.

    Performance on the probabilistic reversal learning task in young and aged rats. A, Aged rats completed fewer reversals over the eight sessions of testing compared with young rats. B, Data from the probabilistic reversal learning task were used to model the choice behavior of rats and to estimate learning rates. Learning rates significantly increased across the eight sessions of testing similarly in young and aged rats. C, The mean number of trials per block decreased across the eight sessions of testing similarly in young and aged rats. D, There was a significant decrease in stochasticity of choice behavior across the eight sessions of training that was evident in both young and aged rats. Data are represented as the mean (±SEM) number of reversals (A) or the learning rate parameters (B–D). *p ≤ 0.05.

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    Figure 5.

    Performance on the progressive ratio schedule of reinforcement assay in young and aged rats. Young rats lever pressed significantly more than aged rats. Data are represented as the mean (±SEM) number of lever presses. *p ≤ 0.05.

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    Figure 6.

    Functional connectivity between region-of-interest pairs in young and aged rats. Aged rats show greater resting-state functional connectivity than young rats among regions known to be critical to decision making under risk of punishment. A, Post hoc analyses indicate significant differences between young and aged functional connectivity for specific region-of-interest pairs. Asterisks denote p ≤ 0.05 after Bonferroni adjustment. B, C, Functional connectome maps of young (left) and aged (right) rats showing rostral-to-caudal (B) and ventral-to-dorsal (C) views of anatomically placed regions and their respective functional connections. Connectome maps were created with BrainNetViewer (Xia et al., 2013). Connecting “edges” are Fisher z-transformed Pearson’s r values.

Tables

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    Table 1

    Mean (±SEM) baseline locomotor activity, locomotor activity during shock delivery, and omissions in the risky decision making task

    Locomotor activity
    (locomotor units/ITI)
    Shock reactivity
    (locomotor units/shock)
    Omissions
    Young9.68 (2.04)2.02 (0.27)1.50 (0.67)*
    Aged6.07 (1.25)1.71 (0.23)7.74 (2.56)*
    • ITI, Intertrial interval.

    • *A main effect of age (p ≤ 0.05).

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    Table 2

    Correlation coefficients comparing risky decision making performance and functional connectivity between region of interest pairs in young and aged rats

    Region of
    interest pair
    GroupSpearman’s ρ correlation
    coefficient
    p-Value†
    BLA.lOFCYoung0.1840.547
    Aged0.10480.911
    BLA.NAcShYoung0.1730.571
    Aged0.2140.610
    BLA.vOFCYoung0.2340.442
    Aged0.0240.955
    lOFC.NAcShYoung0.2340.442
    Aged0.1900.651
    lOFC.PrLYoung0.3820.197
    Aged0.0950.823
    lOFC.vOFCYoung0.2830.348
    Aged−0.0950.823
    BLA.PrLYoung0.4920.087
    Aged0.3570.385
    PrL.NAcShYoung0.3770.204
    Aged−0.0950.823
    PrL.vOFCYoung0.2280.453
    Aged0.0950.823
    PrL.VTAYoung−0.4320.141
    Aged−0.0240.955
    vOFC.NAcShYoung0.4980.083
    Aged0.3810.352
    BLA.VTAYoung0.2040.505
    Aged0.4760.233
    lOFC.VTAYoung0.4700.105
    Aged0.7140.047*
    VTA.NAcShYoung−0.0300.922
    Aged−0.4290.289
    vOFC.VTAYoung0.0830.789
    Aged0.7140.047*
    • *A significant correlation before corrections for multiple comparisons were made (p ≤ 0.05).

    • ↵† p-Values reported without multiple comparisons correction.

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Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model
Caitlin A. Orsini, Wonn S. Pyon, Richard J. Dragone, Mojdeh Faraji, Alexa-Rae Wheeler, Marjory Pompilus, Marcelo Febo, Jennifer L. Bizon, Barry Setlow
eNeuro 3 January 2023, 10 (1) ENEURO.0385-22.2022; DOI: 10.1523/ENEURO.0385-22.2022

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Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model
Caitlin A. Orsini, Wonn S. Pyon, Richard J. Dragone, Mojdeh Faraji, Alexa-Rae Wheeler, Marjory Pompilus, Marcelo Febo, Jennifer L. Bizon, Barry Setlow
eNeuro 3 January 2023, 10 (1) ENEURO.0385-22.2022; DOI: 10.1523/ENEURO.0385-22.2022
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Keywords

  • aging
  • decision making
  • neuroimaging
  • punishment
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