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Research ArticleNew Research, Cognition and Behavior

Optogenetic Dissection of Temporal Dynamics of Amygdala-Striatal Interplay during Risk/Reward Decision Making

Debra A. Bercovici, Oren Princz-Lebel, Maric T. Tse, David E. Moorman and Stan B. Floresco
eNeuro 20 November 2018, 5 (6) ENEURO.0422-18.2018; DOI: https://doi.org/10.1523/ENEURO.0422-18.2018
Debra A. Bercovici
1Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CANADA, V6T 1Z4
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Oren Princz-Lebel
1Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CANADA, V6T 1Z4
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Maric T. Tse
1Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CANADA, V6T 1Z4
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David E. Moorman
2Department of Psychological and Brain Sciences, Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA, USA, 01003
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Stan B. Floresco
1Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CANADA, V6T 1Z4
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  • Figure 1.
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    Figure 1.

    Optogenetic design, histology, and fiber placements for the behavioral experiments. A, Viral infusions were made into BLA, and laser light via optic fibers was delivered to NAc to suppress activity in BLA terminal inputs. B, top panel, Representative slice at 10× of BLA expression within the BLA (blue is DAPI; green is eYFP). Bottom panel, Representative slice at 63× of BLA terminal expression in NAc (blue is DAPI; green is GFP). C, Location of fiber optic placements in NAc. Numbers correspond to mm from bregma.

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    Figure 2.

    Inhibition of BLA terminals in the NAc before choice alters action selection during probabilistic discounting. A, Optogenetic manipulation and task design. Light was delivered at the start of every free choice trial until lever press. B, Percentage choice of the large/risky option under baseline conditions and during optogenetic tests. Inhibition before choice reduced risky choice during the higher, 50% probability block, and increased risky choice in the lower, 12.5% block (n = 16). Inset, Pre-choice optogenetic inhibition increased lose-shift behavior, but did not affect win-stay behavior. C, Individual data, plotted in terms of the percentage of risky choices under baseline and optogenetic test conditions (left panels) and the difference score of these values between baseline and test (right panels). Large circles and bars display the group mean ± SEM for the left and right panels, respectively. In the majority of animals tested, optogenetic inhibition reduced/increased risky choice relative to baseline in the 50%/12.5% probability blocks, respectively. For this and all other figures, error bars are SEM, and stars denote p < 0.05 compared to baseline.

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    Figure 3.

    Inhibition of BLA→NAc pathway after risky losses increases risky choice. A, Optogenetic manipulation and task design. Laser light was delivered for 7 s on trials when the large/risky lever was chosen and no reward was delivered. B, Inhibition during risky losses increased choice of the large/risky option during the low probability block (n = 15). Inset, Win-stay/lose-shift data. The increase in risky choice was not associated with changes in win-stay/lose-shift behavior. C, Individual data. In the majority of rats tested, optogenetic inhibition after risky losses increased risky choice relative to baseline in the 12.5% probability blocks.

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    Figure 4.

    Inhibition of BLA→NAc pathway following rewarded outcomes and during ITI. A, Optogenetic manipulation and task design. Top, Inhibition during large rewards occurred on trials the large/risky lever was chosen and reward was delivered. Bottom, Inhibition during small rewards occurred on trials immediately after the small/certain lever was chosen. B, C, Inhibition of pathway during either large/risky wins (n = 14) or small/safe wins (n = 14) shows no reliable change in choice. D, Optogenetic manipulation during ITI. Light was delivered during every ITI, starting 6–12 s after the end of a trial. E, Optogenetic inhibition during the ITI did not alter choice (n = 12).

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    Figure 5.

    Laser light delivery in control, eYFP-only animals. Laser delivery into NAc (A) during the period before free-choice trials (n = 8) or (B) coinciding with non-rewarded choices (n = 7) did not affect choice. C, Fiber optic placements in the NAc for eYFP-only animals.

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    Figure 6.

    Neurophysiological confirmation of optogenetic inhibition of BLA→NAc inputs. A, Experimental design. Stimulating electrodes were implanted in the BLA and optrode in NAc to record evoked firing of NAc neurons. B, Peristimulus time histograms representing averaged evoked firing rates in 1-ms bins for four neurons (group data) during baseline sweeps (left), sweeps where 10-mW light was applied around the time of BLA stimulation (middle) and recovery (right). Application of light markedly suppressed evoked firing. C, Average percentage change from baseline in BLA-evoked firing probability for rats infused with eArchT in the BLA that received 5- and 10-mW light application, and from control rats infused with eYFP. D, Optrode placements in the NAc. Symbols represent location of last cell recorded from each rat.

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    Table 1

    Performance measures after BLA→NAc optogenetic inhibition during discrete periods of probabilistic discounting

    Mean (SEM)
    ManipulationBaselineBLA→NAc inhibition
    Prior to choice
        Response latency (s)0.51(0.03)0.60*(0.05)
        Number of omissions (over 60 trials)0.40(0.10)0.76*(0.16)
        Locomotion1366(86)1522(109)
    Risky loss
        Response latency (s)0.47(0.03)0.48(0.03)
        Number of omissions (over 60 trials)0.22(0.09)0.23(0.14)
        Locomotion1487(120)1473(119)
    Risky win
        Response latency (s)0.43(0.02)0.43(0.03)
        Number of omissions (over 60 trials)0.11(0.05)0.25(0.13)
        Locomotion1503(163)1560(146)
    Small win
        Response latency (s)0.42(0.03)0.42(0.04)
        Number of omissions (over 60 trials)0.32(0.11)0.18(0.11)
        Locomotion1531(145)1545(143)
    ITI
        Response latency (s)0.40(0.05)0.42(0.07)
        Number of omissions (over 60 trials)0.19(0.12)0.33(0.14)
        Locomotion1720(190)1716(146)
    BaselineeYFP-only rats
    Prior to choice
        Response latency (s)0.62(0.07)0.56(0.08)
        Number of omissions (over 60 trials)0.50(0.16)0.19(0.13)
        Locomotion1290(136)1307(134)
    Risky loss
        Response latency (s)0.55(0.07)0.57(0.06)
        Number of omissions (over 60 trials)0.18(0.14)0.21(0.10)
        Locomotion1559(199)1501(235)
    • Values are displayed as mean (SEM); *p < 0.05 between baseline and pathway inhibition.

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Optogenetic Dissection of Temporal Dynamics of Amygdala-Striatal Interplay during Risk/Reward Decision Making
Debra A. Bercovici, Oren Princz-Lebel, Maric T. Tse, David E. Moorman, Stan B. Floresco
eNeuro 20 November 2018, 5 (6) ENEURO.0422-18.2018; DOI: 10.1523/ENEURO.0422-18.2018

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Optogenetic Dissection of Temporal Dynamics of Amygdala-Striatal Interplay during Risk/Reward Decision Making
Debra A. Bercovici, Oren Princz-Lebel, Maric T. Tse, David E. Moorman, Stan B. Floresco
eNeuro 20 November 2018, 5 (6) ENEURO.0422-18.2018; DOI: 10.1523/ENEURO.0422-18.2018
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Keywords

  • accumbens
  • amygdala
  • decision making
  • Optogenetic inhibition
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