Dissociable Roles for the Nucleus Accumbens Core and Shell in Regulating Set Shifting

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.

Ventral Striatal Dopamine Modulation of Different Forms of Behavioral Flexibility

“…In this study, D 1 antagonism did not increase perseveration, but instead increased regressive errors. This expands on our previous report that NAc core inactivation causes similar, nonperseverative impairments in set-shifting, and further substantiates the notion that neural activity within this nucleus, in conjunction with D 1 receptor tone, facilitates the maintenance of novel strategies once perseveration has ceased (Floresco et al, 2006a). The D 1 antagonist used in these studies (SCH23390) has affinity for both D 1 and 5HT 2A receptors.…”

“…Eight out of every sixteen consecutive trials required the rat to respond in this manner. In a manner similar to that described previously (Ragozzino, 2002;Floresco et al, 2006aFloresco et al, , b, 2008, these trials were separated into consecutive blocks of eight trials each. Perseverative errors were scored when a rat pressed the incorrect lever on six or more out of eight trials per block.…”

“…For example, shifts between stimulus-reward associations within a particular dimension (ie reversal learning) are sensitive to lesions to either the orbitofrontal cortex (OFC) or the dorsal striatum (Divac et al, 1967;Dias et al, 1996;Schoenbaum et al, 2002;Ragozzino et al, 2002;McAlonan and Brown, 2003;Clarke et al, 2008). In rodents, more complex forms of flexibility entailing shifts between rules, strategies, or attentional sets, are dependent on neural circuits incorporating the medial PFC and the core of the nucleus accumbens (NAc) (Reading and Dunnett, 1991;Ragozzino et al, 1999;Birrell and Brown, 2000;Floresco et al, 2006a;Block et al, 2007). Moreover, the cortical and striatal nodes within these circuits appear to make distinct contributions to these processes.…”

“…Disruptions of frontal lobe functioning typically induce perseverative deficits (Ragozzino et al, 1999;Block et al, 2007;Boulougouris et al, 2007). Conversely, manipulations of striatal outputs do not disrupt the ability to disengage from a previously relevant strategy, but do impair maintenance of a novel strategy once perseveration has ceased Floresco et al, 2006a;Block et al, 2007). Dopamine (DA) also is important in facilitating behavioral flexibility mediated by these cortico-striatal circuits.…”

Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats

“…The accumbens nucleus is also involved in spatial behavior and strategy selection. While a functional similarity between the dorsal striatum and accumbens nucleus is demonstrated in the processing of allocentric spatial information, a distinction between the two structures is found in the consolidation of egocentric spatial information (Klein et al 2004;De Leonibus et al 2005;Floresco et al 2006;Haluk and Floresco 2009). Further investigations will be necessary to understand the functional implication of Kv4 channels in the mnesic process, for example, by studying the AmmTX3 infusion effects in these different structures during spatial learning tasks.…”