Dissociable roles for the nucleus accumbens core and shell in regulating set shifting - PubMed (original) (raw)

Dissociable roles for the nucleus accumbens core and shell in regulating set shifting

Stan B Floresco et al. J Neurosci. 2006.

Abstract

The ability to behave in a flexible manner is an executive function mediated in part by different regions of the prefrontal cortex. The present study investigated the role of two major efferents of the prefrontal cortex, the nucleus accumbens (NAc) core and shell, in behavioral flexibility using a maze-based strategy set-shifting task. During initial discrimination training, rats learned to use either an egocentric response or a visual-cue discrimination strategy to obtain food reward. During the set shift, animals had to shift from the previously acquired response or visual-cue-based strategy and learn the alternate discrimination. Inactivation of the NAc core, induced by infusion of the GABA agonists baclofen and muscimol, did not impair initial acquisition of either a response or visual-cue discrimination but severely disrupted shifting from one strategy to another. Analysis of the type of errors revealed that impairments in set shifting were not attributable to increased perseveration but to a disruption of the acquisition and maintenance of a new strategy. In contrast, inactivation of the NAc shell did not impair acquisition of either a response or a visual-cue discrimination, or shifting from one strategy to another. However, inactivation of the NAc shell before initial discrimination training improved performance during the set shift relative to control animals. These data indicate that the NAc core and shell make dissociable contributions to behavioral flexibility during set shifting. The NAc core facilitates the acquisition and maintenance of novel behavioral strategies and elimination of inappropriate response options, whereas the shell may mediate learning about irrelevant stimuli.

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Figures

Figure 1.

Figure 1.

Example of the strategy set-shifting task used in experiments 1A and 2A. The arrows in the maze represent the correct navigation pattern to receive reinforcement. A, During initial response discrimination training on day 1 (top panels), in this example, the rat was started from the south (S), west (W), and east (E) arms and always had to make a 90° turn to the right to receive food reinforcement. A black-and-white-striped visual cue was placed randomly in one of the choice arms on each trial but did not reliably predict the location of food during response training. During the set shift on day 2 (bottom panels), the rat was required to use a visual-cue discrimination strategy. Here, the rat was started from the same arms but had to always enter the arm with visual cue, which could require either a right or left turn. Thus, the rat must shift from the old strategy and approach the previously irrelevant cue to obtain reinforcement.B, Examples of the three types of errors that rats could make during the set shift. See Materials and Methods for details.

Figure 2.

Figure 2.

Schematic of coronal sections of the rat brain showing the placements of the cannula tips for all rats that received infusions of GABA agonists or vehicle into the NAc core (experiment 1; A) or the NAc shell (experiment 2; B). Brain sections correspond to the atlas of Paxinos and Watson (1998).

Figure 3.

Figure 3.

Experiment 1: inactivation of the NAc core disrupts shifting from a response to a visual-cue-based strategy (experiment 1A;A–C) and a visual-cue to a response strategy (experiment 1B; D–F). Data are expressed as means ± SEM. A, Trials to criterion on acquisition of a response discrimination on day 1 by rats receiving infusions of saline (open and filled bars) or baclofen and muscimol into the NAc core (hatched bar). Inactivation of the core did not impair response learning.B, Trials to criterion on the shift to visual-cue discrimination strategy on day 2 after infusions of either saline (open and hatched bars) or baclofen and muscimol into the NAc core (filled bar).★★p < 0.01, significantly different from the saline control group. C, Analysis of the type of errors committed in experiment 1A during the set shift on day 2. Inactivation of the NAc core before the set shift (filled bars) did not alter the number of perseverative errors (left) but increased the number of regressive (middle) and never-reinforced (right) errors.★p < 0.05, significantly different from combined errors made by saline-treated rats (open bars). Inactivation of the core before initial discrimination learning (hatched bars) did not alter the number of errors during the set shift. D, Trials to criterion on acquisition of the visual-cue discrimination on day 1 by rats receiving either infusions of saline (open and filled bars) or baclofen and muscimol into the NAc core (hatched bar). Inactivation of the core did not impair visual-cue-based learning. E, Trials to criterion on the shift to the response discrimination on day 2 after infusions of either saline (open and hatched bars) or baclofen and muscimol into the NAc core (filled bar).★★p < 0.01, significantly different from the saline control group. F, Again, NAc core inactivation did not effect perseveration (left) but increased the number of regressive (middle) and never-reinforced (right) errors during the shift on day 2 (★p < 0.05, significantly different from the same type of errors made by saline-treated rats). Treat, Treatment; Bac/Mus, baclofen/muscimol.

Figure 4.

Figure 4.

Experiment 2: effects of inactivation of the NAc shell on shifting from a response to a visual-cue-based strategy (experiment 2A;A–C) and a visual-cue to a response strategy (experiment 2B; D–F). Data are expressed as means ± SEM. A, Trials to criterion on acquisition of the response discrimination on day 1 by rats receiving either infusions of saline (open and filled bars) or baclofen and muscimol into the NAc shell (hatched bar). Inactivation of the shell did not impair response learning. B, Trials to criterion on the shift to the visual-cue discrimination on day 2 after infusions of either saline (open and hatched bars) or baclofen and muscimol into the NAc shell (filled bar). NAc shell inactivation before the set shift did not impair performance. However, rats receiving inactivation of the shell on day 1 and saline infusions on day 2 (hatched bar) displayed improved performance during the set shift.★★p < 0.01, significantly different from the saline control group. C, Analysis of the type of errors committed in experiment 2A during the shift on day 2. Inactivation of the NAc shell on day 1 (hatched bars) resulted in fewer perseverative (left) and regressive (middle) errors during the set shift on day 2.★p < 0.05, significantly different from the same type of errors made by saline-treated rats (open bars). Inactivation of the shell before the set shift (filled bars) did not alter the number of errors.D, Trials to criterion on acquisition of the visual-cue discrimination on day 1 by rats receiving either infusions of saline (open and filled bars) or baclofen and muscimol into the NAc shell (hatched bar). Inactivation of the shell did not impair visual-cue-based learning.E, Trials to criterion on the shift to the response discrimination on day 2 after infusions of either saline (open and hatched bars) or baclofen and muscimol into the NAc shell (filled bar). NAc shell inactivation did not impair set shifting. However, as observed in experiment 2A, inactivation of the shell on day 1 (hatched bar) improved performance during the set shift. ★★p < 0.01, significantly different from the saline control group. F, Histogram displaying the type of errors committed in experiment 2B during the shift on day 2 by each group of rats. Treat, Treatment; Bac/Mus, baclofen/muscimol.

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