Prelimbic/infralimbic inactivation impairs memory for multiple task switches, but not flexible selection of familiar tasks

Abstract

Behavioral flexibility, in the form of strategy switching or set shifting, helps animals cope with changing contingencies in familiar environments. The prelimbic (PL) and infralimbic (IL) regions of the rat prefrontal cortex (PFC) contribute to this ability so that rats trained to use one strategy have difficulty learning a new one if the PL/IL is inactivated. Thus, the PL/IL mediates learning new tasks in place of old ones, but it may also be required to switch between familiar tasks. To test this hypothesis, we trained rats to perform multiple task switches on a plus-shaped maze, alternating between two familiar tasks. Muscimol inactivation of the PL/IL never impaired switch acquisition, but did impair memory for the recently acquired switch 24 h later. Additional experiments determined that control rats continued to perform the new task 24 h after a switch, but rats with PL/IL inactivation had impaired memory and performed the same task that was learned before inactivation. This impairment was observed in multiple switches, demonstrating that PL/IL activity was required to remember which of two familiar tasks was most recently successful. After many switches, however, muscimol no longer impaired performance, and both saline- and muscimol-infused rats appeared to use immediate task contingencies rather than memory to select among familiar tasks. This strategy may account for the decreased effect of PL/IL inactivation observed after extensive training. Thus, although PL/IL activity contributed to memory for multiple task switches, it was not required for flexibly selecting among highly familiar tasks.

Figure 1.

Cannula locations. a, Coronal sections +3.7 to +2.7 mm from bregma are reproduced (Paxinos, 1986) with symbols indicating cannula tips for each rat. Gray circles, Muscimol infusions in the switch group of experiment 1; white circles, saline infusions in the switch group of experiment 1; gray stars, muscimol infusions in the reversal group of experiment 1; white stars, saline infusions in the reversal group of experiment 1; gray squares, experiments 3 and 4 (drug infusions were counterbalanced between rats). b, A representative Nissl-stained section through the PL/IL. The black arrow indicates the end of a larger diameter track from the guide cannula, and the circle indicates the tip of the internal cannula.

Figure 2.

Experimental design. Five experiments were performed. All animals were initially treated similarly (all experiments). To test PL/IL involvement in switching between familiar tasks, experiment 1 tested separate groups of rats in either 12 switches (S) between place and response tasks or 12 spatial reversals (R) over many days. Infusions of either muscimol or saline were delivered before some S/Rs (shaded blocks), but not others (unshaded blocks). TTC was measured for all S/R blocks and errors were measured during the T = 0 (T0) and T = 24 (T24) blocks. Blocks in the same column represent measurements taken sequentially on the same day, and columns represent separate days (left to right). In experiment 2, rats that had performed spatial reversals in experiment 1 (gray arrow to reversal group) were required to perform a switch to test for nonspecific effects of repeated infusions in the previous experiment. In experiments 3 and 4, a separate group of rats performed three switches. Infusions were delivered after the first switch (experiment 3) to test the temporal requirements for PL/IL activity. To determine whether saline and muscimol-infused rats perform the most recently used maze task 24 h after a switch, experiment 4 tested animals on a double switch (DS) in which they switched tasks on day 1, but were tested 24 h later on the other, preswitch task. Experiment 5 tested rats that had performed 12 switches in experiment 1 (gray arrow to switch group) in the DS.

Figure 3.

Place and response tasks on the plus-shaped maze. In the place task, one goal arm (north or south) was approached from both start arms (east and west). In the response task, one body turn response (right or left) was made to enter a goal arm from either start arm. Black arrows depict correct journeys from each start arm. Each rat learned only two of the four possible contingencies. Switching rats learned one place and one response contingency, whereas rats performing spatial reversals learned both place contingencies (see Experiment 1: multiple switches versus multiple reversals).

Figure 4.

Experiment 1. a–c, TTC (±SEM; a), errors at T = 0 (±SEM; b), and errors at T = 24 (±SEM; c) for serial task switches. Rats were infused with muscimol (black lines) or saline (gray lines) before some switches and reversals (solid lines) but not others (dashed lines). The drug infusion had no effect on any group in TTC or errors at T = 0. Only rats given muscimol before switching were impaired at T = 24 (solid black line), and this effect decreased over time. *p < 0.05.

Figure 5.

Experiment 2: errors at T = 24. Errors at T = 24 (±SEM) after spatial reversal experts performed a switch are shown. Muscimol (gray) or saline (white) infusions were given before learning the switch. Muscimol significantly increased errors at T = 24, but not TTC or errors at T = 0 (data not shown). *p < 0.05.

Figure 6.

Experiment 3: errors at T = 24. Errors at T = 24 (±SEM) after switching in rats infused with muscimol (gray) or saline (white) either before (solid; data from Experiment 1) or immediately after (hatched) the switch are shown. Rats were significantly impaired at T = 24 only when infused with muscimol before switching. *p <0.05.

Figure 7.

Experiments 4 and 5: errors at T = 24. Errors at T = 24 (±SEM) when rats performed a switch (solid bars, data from Experiment 1) or double switch (hatched bars) are shown. Infusions of muscimol (gray) or saline (white) were given. a, In experiment 4, rats with less switching experience made more errors when infused with muscimol before switching (gray solid bars) or when infused with saline before a double switch (white hatched bars). Neither drug nor test type altered TTC or errors at T = 0 (data not shown). b, In experiment 5, rats that were highly familiar with both tasks made few errors, regardless of infusion or switch type. *p < 0.05.