Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning

Ghods-Sharifi, Sarvin; Haluk, Desirae M.; Floresco, Stan

doi:10.1016/j.nlm.2007.10.007

Cited by 163 publications

(126 citation statements)

References 18 publications

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“…Other studies [7,10] have assessed the effects of acute stress on reversal learning using a lever-based operant task that is typically completed by rats in a single day [16,23]. In one study, a single restraint stress session before reversal learning facilitated reversal learning but not set-shifting [10].…”

Section: Discussionmentioning

confidence: 99%

“…Reversal learning, a type of behavioral flexibility that requires a change in strategy based on one dimension of the stimuli, is partly mediated by the orbitofrontal cortex [11,16]. Reversal learning assayed using operant-based tasks is facilitated following an acute (1 day) or subchronic (3 days) stressor in most [10][11][12] but not all studies [7].…”

Section: Introductionmentioning

confidence: 99%

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Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

Bryce

Howland

2015

Behavioural Brain Research

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The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibility that is facilitated following some brief stress procedures. The current study investigated a potential mechanism underlying this facilitation by blocking glucocorticoid receptors (GRs) during stress. Thirty-seven male Long Evans rats learned to discriminate between two images on a touchscreen, one of which was rewarded. Once a criterion was reached, rats received stress (30 min of restraint stress or no stress) and drug (GR antagonist RU38486 or vehicle) administration prior to each of the first 3 days of reversal learning. We expected that stress would facilitate reversal learning and RU38486 (10 mg/kg) would prevent this facilitation in both early (<50% correct in one session) and late (>50% correct in one session) stages of reversal learning. Results showed that stressed rats performed better than unstressed rats (fewer days for late reversal, fewer correction trials, and fewer errors) in the late but not early stage of reversal learning. RU38486 did not block the facilitation of RL by stress, although it dramatically increased response, but not reward, latencies. These results confirm the facilitation of late reversal by stress in a touchscreenbased operant task in rats and further our understanding of how stress affects higher level cognitive functioning and behavior.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

Bryce

Howland

2015

Behavioural Brain Research

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“…The present results suggest that dopaminergic modulation of reversal learning likely occurs through actions on D 2 receptors located in regions other than the NAc. In this regard, although the OFC is critical in facilitating reversal shifts (Dias et al, 1996;McAlonan and Brown, 2003;Ragozzino, 2007;Ghods-Sharifi et al, 2008), mesocortical DA depletion does not affect this form of flexibility (Crofts et al, 2001). The possibility remains that the certain subregions of the dorsal striatum may be the critical locus where D 2 receptors enable shifts between different stimulus-reward contingencies, although striatal DA depletion has yielded inconsistent effects on reversal learning (Collins et al, 2000;Crofts et al, 2001;O'Neill and Brown, 2007).…”

Section: A Selective Role For Nac D 1 Receptors In Strategy Set-shiftingmentioning

confidence: 99%

Ventral Striatal Dopamine Modulation of Different Forms of Behavioral Flexibility

Haluk

Floresco

2009

Neuropsychopharmacol

181

174

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Different forms of behavioral flexibility are facilitated by interactions between separate regions of the prefrontal cortex and their striatal outputs. However, the contribution of ventral striatal dopamine (DA) to these functions is unclear. The present study assessed the involvement of DA receptors in the nucleus accumbens (NAc) core on either between-or within-strategy shifts using operant chamberbased tasks. Strategy set-shifting required rats initially to learn a visual-cue discrimination and, on the following day, shift to using an egocentric spatial response strategy to obtain reward. For reversal learning, rats were initially trained on a response discrimination and then required to select the opposite lever to receive food reward. Intra-NAc microinfusions of D 1 (SCH23390) but not D 2 (eticlopride) receptor antagonists impaired set-shifting, disrupting the maintenance of a new strategy. Conversely, supranormal activation of D 2 (quinpirole) but not D 1 (SKF81297) receptors also impaired set-shifting, inducing perseverative deficits. However, only infusions of the D 2 agonist impaired reversal learning, but did so without disrupting initial response learning. Thus, mesoaccumbens DA, acting on D 1 receptors, selectively facilitates complex forms of flexibility requiring shifts between different strategies, but does not appear to contribute to simpler forms of flexibility entailing shifts of specific stimulus-reward associations. In contrast, abnormal increases in D 2 receptor activity cause a more general impairment in behavioral flexibility. These findings suggest that deficits in these forms of executive functioning observed in disorders linked to dysfunction of the DA system may be attributable in part to aberrant increases or decreases in mesoaccumbens DA activity.

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“…The literature from humans, primates, and rodents (Dalley et al, 2004;Ghods-Sharifi et al, 2008;Rygula et al, 2010) indicates a critical role for the orbitofrontal cortex (OFC) in mediating the behavioral flexibility required for reversal learning, whereas the integrity of the PFC (Birrell and Brown, 2000;Robbins, 2007;Stefani and Moghaddam, 2005), with modulation from the NAC (Floresco et al, 2006), determines the ability to learn an ED shift. Efferents from the subicular region of the VH project directly onto interneuron and pyramidal target neurons in the PFC (Jay et al, 1989;Tierney et al, 2004) or indirectly to PFC via projections to NAC (French and Totterdell, 2003;Miller et al, 2010) and then through BF (Henny and Jones, 2008) or medial dorsal thalamus (Sarter & Markowitsch, 1984).…”

Section: Potential Mechanisms Contributing To Set-shifting Deficitsmentioning

confidence: 99%

Transient Inactivation of the Neonatal Ventral Hippocampus Impairs Attentional Set-Shifting Behavior: Reversal with an α7 Nicotinic Agonist

Brooks

Pershing

Thomsen

et al. 2012

Neuropsychopharmacol

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Cognitive deficits represent a core symptom cluster in schizophrenia that are thought to reflect developmental dysregulations within a neural system involving the ventral hippocampus (VH), nucleus accumbens (NAC), and prefrontal cortex (PFC). The present experiments determined the cognitive effects of transiently inactivating VH in rats during a sensitive period of development. Neonatal (postnatal day 7, PD7) and adolescent (PD32) male rats received a single bilateral infusion of saline or tetrodotoxin (TTX) within the VH to transiently inactivate local circuitry and efferent outflow. Rats were tested as adults on an attentional set-shifting task. Performance in this task depends upon the integrity of the PFC and NAC. TTX infusions did not affect the initial acquisition or ability to learn an intradimensional shift. However, TTX rats required a greater number of trials than did controls to acquire the first reversal and extradimensional shift (ED) stages. These impairments were age and region-specific as rats infused with TTX into the VH at PD32, or into the dorsal hippocampus at PD7, exhibited performance in the task similar to that of controls. Finally, acute systemic administration of the partial a7 nicotinic acetylcholine receptor (nAChR) agonist SSR 180711 (3.0 mg/kg) eliminated the TTX-induced performance deficits. Given that patients with schizophrenia exhibit hippocampal pathophysiology and deficits in the ED stages of set-shifting tasks, our results support the significance of transient hippocampal inactivation as an animal model for studying the cognitive impairments in schizophrenia as well as the pro-cognitive therapeutic potential of a7 nAChR agonists.

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Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning

Cited by 163 publications

References 18 publications

Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

Ventral Striatal Dopamine Modulation of Different Forms of Behavioral Flexibility

Transient Inactivation of the Neonatal Ventral Hippocampus Impairs Attentional Set-Shifting Behavior: Reversal with an α7 Nicotinic Agonist

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