Dorsolateral striatum engagement during reversal learning

Abstract

Most experimental preparations demonstrate a role for dorsolateral striatum (DLS) in stimulus-response, but not outcome-based, learning. Here, we assessed DLS involvement in a touchscreen-based reversal task requiring mice to update choice following a change in stimulus-reward contingencies. In vivo single-unit recordings in the DLS showed reversal produced a population-level shift from excited to inhibited neuronal activity prior to choices being made. The larger the shift, the faster mice reversed. Furthermore, optogenetic photosilencing DLS neurons during choice increased early reversal errors. These findings suggest dynamic DLS engagement may facilitate reversal, possibly by signaling a change in contingencies to other striatal and cortical regions.

Figure 1.

DLS neuronal recordings in a pairwise discrimination and reversal touchscreen task. (A) Mice had microarray electrode arrays unliterally implanted in the DLS (dots depict estimated location of arrays) and were trained to discriminate between two visual stimuli (“fan” and “marble”) presented on a touch-sensitive screen to obtain a food pellet. The stimulus-reward contingency was then reversed, and mice retrained to criterion. DLS neuronal activity was recorded on three sessions: late discrimination (^LD), early reversal (^ER), and late reversal (^LR). (B) Discrimination and reversal criteria (>85% correct choice) were attained in ∼12–14 test sessions. (C) Percent correct choice was high at ^LD and ^LR, and low at ^ER (repeated ANOVA stage effect: F_(2,24) = 129.56, P < 0.01, followed by Newman-Keuls post hoc tests). Errors were low at ^LD and ^LR, and high ^ER, whether measured as total errors (F_(2,24) = 26.41, P < 0.01) (D), perseverative errors (an error following an error) (F_(2,24) = 26.33, P < 0.01) (E) or nonperseverative errors (an error following a correct) (F_(2,24) = 15.43, P < 0.01) (F). For corresponding choice and reward-collection latencies, see Supplemental Figure S1. n = 13 mice. Data are means ± SEM. (*) P < 0.05.

Figure 2.

DLS neuronal activity changes on reversal. (A) Raster and perievent histogram examples of DLS neurons exhibiting increased (“excited,” red shading) or decreased (“inhibited,” blue shading) activity either prior to or immediately after a choice was made. (B) On the ^LD recording session, the majority of (pre or post) choice related DLS neurons were excited. This pattern was maintained for postchoice neurons on the ^ER and ^LR recording sessions (χ² comparison ^ER versus ^LD: P > 0.05; ^LR versus ^LD: P > 0.05). Conversely, there was a significant shift increase in the proportion of inhibited prechoice neurons at ^ER, which was maintained at ^LR (^ER versus ^LD: χ² = 21.95, P < 0.01; ^LR versus ^ER: χ² = 10.32, P < 0.01), and a corresponding decrease in excited neurons (^ER versus ^LD: χ² = 5.02, P < 0.05; ^LR versus ^ER: χ² = 9.47, P < 0.01). (C) The proportion of DLS neurons exhibiting prechoice inhibited activity at ^ER predicted fewer sessions to reach reversal criterion. (D) Segregation of slow and fast learners based on a median split of sessions to reversal criterion. Slow learners made more errors during reversal (t₍₉₎ = 2.38, P < 0.05) (E) but showed similar latencies to choose (t₍₉₎ = 0.69, P > 0.05) and collect reward (t₍₉₎ = 1.13, P > 0.05) (F), as compared to fast learners. (G) Slow learners had a significantly small proportion of prechoice inhibited DLS neurons than fast leaners at ^ER (t₍₉₎ = 3.49, P < 0.01), but not other stages. Data are means ± SEM. Data are means ± SEM. (*) P < 0.05.

Figure 3.

Optogenetic silencing of DLS disrupts early reversal. (A) DLS photosilencing during touchscreen reversal learning. (B) DLS-silencing did not affect the number of sessions to attain reversal criterion (unpaired Student's t-test: t₍₁₃₎ = 0.94, P > 0.05) or (C) correct responding at any stage of reversal (ANOVA group-effect: F_(1,13) = 1.61, P > 0.05; stage-effect: F_(2,26) = 177.15, P < 0.01; interaction: F_(2,26) = 0.42, P > 0.05). (D) Silencing did, however, increase the number of total errors made, specifically at ^ER (ANOVA group-effect: F_(1,13) = 0.76, P > 0.05; stage-effect: F_(2,26) = 134.83, P < 0.01; interaction: F_(2,26) = 8.71, P < 0.01). (E) This effect was largely driven more perseverative errors (ANOVA group-effect: F_(1,13) = 1.03, P > 0.05; stage-effect: F_(2,26) = 203.78, P < 0.01; interaction: F_(2,26) = 9.93, P < 0.01), (F) though nonperseverative errors were also visibly higher (ANOVA group-effect: F_(1,13) = 0.32, P > 0.05; stage-effect: F_(2,26) = 14.24, P < 0.01; interaction: F_(2,26) = 3.39, P < 0.05). n = 7–8 per group. Data are means ± SEM. (*) P < 0.05.