Touchscreen-based assessment of risky-choice in mice

Abstract

Addictions are characterized by choices made to satisfy the addiction despite the risk it could produce an adverse consequence. Here, we developed a murine version of a 'risky decision-making' task (RDT), in which mice could respond on a touchscreen panel to obtain either a large milkshake reward associated with varying probability of footshock, or a smaller amount of the same reward that was never punished. Results showed that (the following font is incorrectly smaller/subscripted) mice shifted choice from the large to small reward stimulus as shock probability increased. Immunohistochemical analysis revealed more Fos-positive cells in prelimbic cortex (PL) and basal amygdala (BA) after RDT testing, and a strong anti-correlation between infralimbic cortex (IL) activity and choice of the large reward stimulus under likely (75-100 % probability) punishment. These findings establish an assay for risky choice in mice and provide preliminary insight into the underlying neural substrates.

Keywords: addiction; amygdala; prefrontal; punishment; risky; touchscreen.

Figure 1:. Touchscreen-based risky decision-making task (RDT) for mice.

(A) Sequence of experimental stages. (B) Mouse-eye view of the choice-stimuli displayed on the touchscreen. Large and small reward options. (C) During RDT training, response on the left versus right stimulus produces the large or small reward, respectively. (D) During RDT testing, response on the left versus right stimulus produces the large reward and possible shock or small reward and no shock, respectively.

Figure 2:. Schematics of task-flow during RDT training and testing.

(A) Task-flow on forced and choice trials during RDT training. (B) RDT training sessions comprise 40-forced trials followed by 50 choice-trials. (C) Task-flow on forced and choice trials during RDT testing. (D) RDT training sessions comprise 5 successive blocks of 8-forced trials followed by 10 choice-trials, in which shock-probability following a large reward choice increases in 25% increments.

Figure 2:. Schematics of task-flow during RDT training and testing.

(A) Task-flow on forced and choice trials during RDT training. (B) RDT training sessions comprise 40-forced trials followed by 50 choice-trials. (C) Task-flow on forced and choice trials during RDT testing. (D) RDT training sessions comprise 5 successive blocks of 8-forced trials followed by 10 choice-trials, in which shock-probability following a large reward choice increases in 25% increments.

Figure 3:. Performance during RDT testing.

(A) Reward preference shifts from the large to small reward option with increasing probability the large reward option will result in shock. (B) Increased omission rate at the 75% shock-probability block. (C) Increased latency to choose the large reward stimulus at the 75% shock-probability block. #versus small reward on same shock-probability block. n=11. Data are means ± SEM.

Figure 4:. IEG activity associated with RDT testing.

(A) Immunohistochemical labeling and quantification of Fos-positive cells was conducted after RDT testing or a non-shocked (NS) RDT testing equivalent session. (B) Higher Fos counts in PL after RDT. (C) No difference in Fos counts in IL. (D) Higher Fos counts in BA after RDT. (E) Lower Fos counts in mHb after RDT. (F) No difference in Fos counts in lHb. (G) Fos counts in IL anti-correlate with large reward choice during the 75% and 100% shock-probability blocks. *versus NS. n=11 RDT, n=4 NS. Data are means ± SEM.