Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning

Abstract

The present experiments investigated the role of the prelimbic-infralimbic areas in behavioral flexibility using a place-response learning paradigm. All rats received a bilateral cannula implant aimed at the prelimbic-infralimbic areas. To examine the role of the prelimbic-infralimbic areas in shifting strategies, rats were tested on a place and a response discrimination in a cross-maze. Some rats were tested on the place version first followed by the response version. The procedure for the other rats was reversed. Infusions of 2% tetracaine into the prelimbic-infralimbic areas did not impair acquisition of the place or response discriminations. Prelimbic-infralimbic inactivation did impair learning when rats were switched from one discrimination to the other (cross-modal shift). To investigate the role of the prelimbic-infralimbic areas in intramodal shifts (reversal learning), one group of rats was tested on a place reversal and another group tested on a response reversal. Prelimbic-infralimbic inactivation did not impair place or response intramodal shifts. Some rats that completed testing on a particular version in the cross-modal and intramodal experiments were tested on the same version in a new room for 3 d. The transfer tests revealed that rats use a spatial strategy on the place version and an egocentric response strategy on the response version. Overall, these results suggest that the prelimbic-infralimbic areas are important for behavioral flexibility involving cross-modal but not intramodal shifts.

Fig. 1.

Example of a rat tested on the place and response discriminations. In the place version, this rat was started from the S and W arms and always had to enter the N arm to receive a cereal reinforcement. In the response version, this rat was started from the E and W arms and always had to turn right to receive a cereal reinforcement. The arrows in the maze represent the correct navigation patterns to receive a reinforcement. ●, Food well containing cereal reinforcement.

Fig. 2.

The black areas represent the location of the injection cannula tips in the prelimbic–infralimbic cortices for all rats included in the behavioral analyses. Rat brain sections were adapted from Paxinos and Watson (1986).

Fig. 3.

A, Mean trials to criterion on acquisition of the place discrimination after vehicle or 2% tetracaine infusions into the prelimbic–infralimbic areas. The treatment received on this test is underlined for each group.VEH, Saline; TET, 2% tetracaine.B, Mean trials to criterion on the shift to a response discrimination after vehicle or 2% tetracaine infusions into the prelimbic–infralimbic areas. The treatment received on this test isunderlined for each group. *p < 0.05 versus vehicle-injected groups. C, Mean number of trials to perseverate and complete learning on the shift to a response discrimination after vehicle or 2% tetracaine injections into the prelimbic–infralimbic areas. ■, VEH- VEH; ▨, VEH- TET; ▧, TET- VEH.Underlined is the treatment received during the response discrimination. *p < 0.05 versus vehicle-injected controls.

Fig. 4.

A, Mean trials to criterion on acquisition of the response discrimination after vehicle or 2% tetracaine infusions into the prelimbic–infralimbic areas. The treatment received on this test is underlined for each group. VEH, Saline; TET, 2% tetracaine.B, Mean trials to criterion on the shift to a place discrimination after vehicle or 2% tetracaine infusions into the prelimbic–infralimbic areas. The treatment received on this test isunderlined for each group. *p < 0.05 versus vehicle-injected groups. C, Mean number of trials to perseverate and complete learning on the shift to a place discrimination after vehicle or 2% tetracaine injections into the prelimbic–infralimbic areas. ■, VEH- VEH; ▨, VEH- TET; ▧, TET- VEH.Underlined is the treatment received during the place discrimination. *p < 0.05 versus vehicle-injected groups.

Fig. 5.

A, Mean trials to criterion on acquisition and reversal of the place discrimination after vehicle or 2% tetracaine infusions into the prelimbic–infralimbic areas.VEH, Saline; TET, 2% tetracaine.B, Mean number of trials to perseverate and complete learning on reversal of the place discrimination after vehicle or 2% tetracaine infusions into the prelimbic–infralimbic areas.

Fig. 6.

A, Mean trials to criterion on acquisition and reversal of the response discrimination after vehicle or 2% tetracaine infusions into the prelimbic–infralimbic areas.VEH, Saline; TET, 2% tetracaine.B, Mean number of trials to perseverate and complete learning on reversal of the response discrimination after vehicle or 2% tetracaine infusions into the prelimbic–infralimbic areas.

Fig. 7.

Mean percent correct in the place discrimination during the last test session in the first room and the subsequent three test sessions that occurred in a new room after vehicle or 2% tetracaine injections into the prelimbic–infralimbic areas.Symbols representing the FIRST ROOM data: ■, vehicle or 2% tetracaine; ○, vehicle.

Fig. 8.

Mean percent correct in the response discrimination during the last test session in the first room and the subsequent three test sessions that occurred in a new room after vehicle or 2% tetracaine injections into the prelimbic–infralimbic areas. Symbols representing the FIRST ROOM data: ■, vehicle or 2% tetracaine; ○, vehicle.