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.

Introduction

Historically, the nucleus accumbens (NAc) has been considered a site of “limbic–motor integration” important for the ability of motivationally significant stimuli to guide goal-directed behavior [1], [2], [3]. The NAc and its subnuclei, the core and shell, are involved in a variety of appetitive behaviors [4], [5], [6], [7], [8], [9], [10]. In a type of appetitive Pavlovian conditioning called Pavlovian conditioned approach (PCA), repeated pairing of a conditioned stimulus (CS) with the delivery of a reward can induce multiple conditioned responses during CS presentation, including approach to both the CS and the site of unconditioned stimulus (US) delivery [3], [11]. Conditioned approaches to the site of US delivery are known as goal-tracking [12].

Memory consolidation refers to the biological stabilization of long-term memories, and in rodents, this process is generally thought to occur during several hours immediately following memory acquisition [13], [14], [15]. Experimentally, memory consolidation can be differentiated from memory acquisition through the timing of experimental manipulations; pre-training manipulations are thought to affect memory acquisition while post-training manipulations are thought to affect memory consolidation [13], [14]. We demonstrated previously that inhibition of protein synthesis impairs consolidation of the goal-tracking form of PCA [16], but the location of this consolidation-related protein synthesis is unknown.

There is evidence that the NAc shell, but not the core, is involved in the consolidation, but not the acquisition, of goal-tracking PCA. Post-training infusions of the psychostimulant d-amphetamine in the full NAc as well as the NAc shell enhanced goal-tracking PCA, suggesting that the shell is involved in consolidation, but infusions of d-amphetamine in the core had no effect [17]. In addition, pre-training lesions of the NAc core and NAc shell had no effect on acquisition of goal-tracking PCA, and pre-training lesions that contralaterally disconnected the NAc and basolateral amygdala had no effect on the acquisition of first-order conditioning (although second-order conditioning was impaired), suggesting that the NAc is not necessary for PCA acquisition [18], [19]. However, there is evidence that the NAc is necessary for the expression of goal-tracking PCA, as pre-test lesions of the NAc core (but not the shell) have been shown to impair the expression of this behavioral task [20].

To further elucidate the role of the NAcc core and shell in goal-tracking PCA, we have examined the effect of reversible inactivation of these brain regions on the consolidation and expression of a goal-tracking PCA task. Additionally, we have used the protein synthesis inhibitor anisomycin (ANI) to investigate whether protein synthesis-dependent plasticity is necessary within these brain regions for the consolidation of the PCA memory.