The nucleus accumbens core and shell are critical for the expression, but not the consolidation, of Pavlovian conditioned approach

Abstract

The nucleus accumbens (NAc) is important for the ability of motivationally significant stimuli to guide behavior. To further delineate its role in appetitive Pavlovian conditioning, we tested the hypothesis that the NAc contributes to memory consolidation and expression for a goal-tracking version of Pavlovian conditioned approach (PCA) in rats. We found that neither post-training reversible inactivation with the GABA receptor agonists muscimol and baclofen nor inhibition of protein synthesis with anisomycin (ANI) in either the core or shell regions of the NAc had an effect on approach to a reward port in response to a reward-predictive cue (conditioned stimulus, CS+). In contrast, pre-test reversible inactivation of both the core and shell decreased conditioned responding during the CS+. Unlike inactivation of the core, however, reversible inactivation of the shell also produced an increase in responding during the CS- and the inter-trial interval. This suggests that the NAc is not involved in the consolidation of goal-tracking PCA, but that once the memory is formed, the core is required for expression of the CS-unconditioned stimulus (US) association and the shell is required to inhibit conditioned approach behavior at times when the CS+ is not presented.

Figure 1. Schematic representation of cannula placements for rats that received post-training reversible inactivation

a) Cannula placements for rats that received post-training infusions of vehicle or M/B in the NAc core. Coordinates are A/P from Bregma. b) Cannula placements for rats that received post-training infusions of vehicle of M/B in the NAc shell. Coordinates are A/P from Bregma.

Figure 2. Reversible inactivation of the NAc does not affect the consolidation of PCA behavior

a) Experimental design. b) Mean difference score ± SEM during PCA training sessions for rats that received infusions into the NAc core (Vehicle: n=6; M/B: n=7). The difference score reported in this and the following figures represents the number of port entries during the CS+ minus the number of port entries during the CS−. c) Mean difference score ± SEM during PCA training sessions for rats that received infusions into the NAc shell (Vehicle: n=7; M/B: n=8). d) Mean number of port entries (± SEM) exhibited during stimulus presentations in the 4^th PCA training session for rats that received infusions in the NAc core. “Pre-CS+” = the 10 sec preceding the onset of the CS+. e) Mean number of port entries (± SEM) exhibited during stimulus presentations in the 4^th PCA training session for rats that received infusions in the NAc shell. “Pre-CS+” = the 10 sec preceding the onset of the CS+.

Figure 3. Schematic representation of cannula placements for rats that received post-training inhibition of protein synthesis

a) Cannula placements for rats that received post-training infusions of vehicle or ANI in the NAc core. Coordinates are A/P from Bregma. b) Cannula placements for rats that received post-training infusions of vehicle or ANI in the NAcc shell. Coordinates are A/P from Bregma.

Figure 4. Protein synthesis inhibition within the NAc does not affect the consolidation of PCA behavior

a) Experimental design. b) Mean difference score ± SEM during PCA training sessions for rats that received infusions into the NAc core (Vehicle: n=12; Ani: n=11). c) Mean difference score ± SEM during PCA training sessions for rats that received infusions into the NAc shell (Vehicle: n=6; Ani: n=6). d) Mean number of port entries (± SEM) exhibited during stimulus presentations in the 4^th PCA training session for rats that received infusions in the NAc core. “Pre-CS+” = the 10 sec preceding the onset of the CS+. e) Mean number of port entries (± SEM) exhibited during stimulus presentations in the 4^th PCA training session for rats that received infusions in the NAc shell. “Pre-CS+” = the 10 sec preceding the onset of the CS+.

Figure 5. Schematic representation of cannula placements for rats that received pre-test reversible inactivation

a) Cannula placements for rats that received pre-test infusions of vehicle and M/B in the NAc core. Note that there is only one group of rats because this was a within-subjects study. Coordinates are A/P from Bregma. b) Cannula placements for rats that received pre-test infusions of vehicle and M/B in the NAc shell. Note that there is only one group of rats because this was a within-subjects study. Coordinates are A/P from Bregma.

Figure 6. Reversible inactivation of the NAc impairs the expression of PCA behavior

a) Experimental design. b) Mean difference score (± SEM) during PCA training and test sessions for rats that received infusions into the NAc core (n=15). **P<.01. c) Mean difference score (± SEM) during PCA training and test sessions for rats that received infusions into the NAc shell (n=8). **P<.01. d) and e) Port entries exhibited by representative rats. The top half of each graph is a perievent raster in which each horizontal row of tick marks represents a separate trial during the training/test session, each individual tick mark represents a single port entry, black circles represent the onset of the CS+, and black triangles represent the offset of the CS+ and onset of the pump that delivered the sucrose reward. The bottom half of each graph is a perievent histogram showing the total number of port entries (during 2 sec bins) made during all trials of the training/test session. The zero time point on the histogram represents the onset of the CS+. The panels on the left depict port entries made during the first training session; the middle panels depict port entries made during the test session immediately after vehicle infusion; and, the panels on the right depict port entries made during the test session immediately after M/B infusion. d) Port entries by a representative rat that received infusions in the NAc core. e) Port entries by a representative rat that received infusions in the NAc shell. f) Mean number of port entries (± SEM) during PCA test session stimulus presentations for rats that received infusions in the NAc core. “Pre-CS+” = the 10 sec preceding the onset of the CS+. *P<.05. g) Mean number of port entries (± SEM) during PCA test session stimulus presentations for rats that received infusions in the NAc shell. “Pre-CS+” = the 10 sec preceding the onset of the CS+. *P<.05, **P<.01. h) Mean number of port entries (± SEM) during the entire 90 min PCA test session. **P<.01. i) Mean number of trials (± SEM) in the PCA test session for which there was a response to US (sucrose) delivery.