Schoenbaum G, Nugen SL, Saddoris ML, Setlow B. Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations. Neuroreport 13: 885-890

Department of Psychological and Brain Sciences, Johns Hopkins University, 3400 North Charles Street, 25 Ames Hall, Baltimore, MD 21218, USA.
Neuroreport (Impact Factor: 1.52). 06/2002; 13(6):885-90. DOI: 10.1097/00001756-200205070-00030
Source: PubMed


Recent evidence suggests that orbitofrontal cortex lesions cause an inability to withhold inappropriate responses particularly when learned behavior must be modified to reflect changes in the likely outcome or consequence of responding. By this account, orbitofrontal cortex should not be necessary for acquisition of simple discrimination problems, but should be critical for acquiring reversals of those problems. However, previous work in rats has shown orbitofrontal cortex to be critical for withholding responses even in a simple go, no-go discrimination task. Here we have reexamined the contribution of rat orbitofrontal cortex to acquisition and reversal of go, no-go odor discrimination problems. Contrary to prior reports, we found that rats with lesions of the orbitofrontal cortex acquired novel discrimination problems at the same rate as controls. Impairments were evident in lesioned rats when the response contingencies of the odors in the discrimination problem were reversed. These findings suggest that orbitofrontal cortex is not necessary for inhibiting responses unless responses must be altered to reflect changing relationships between cues and outcomes.


Available from: Geoffrey Schoenbaum
  • Source
    • "This conclusion is also supported by the fact that atomoxetine does not affect probabilistic learning in humans (Chamberlain et al. 2006). Additionally, reversals, which isolate the use of outcomes to change behavior while keeping stimuli constant, depend on different PFC sub-regions in comparison to attentional set shifting and depends upon PFC serotonin neurotransmission rather than NE and DA (Dias et al. 1996; Birrell and Brown 2000; Schoenbaum et al. 2002). Therefore, it is unlikely that atomoxetine affected processing of outcomes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Shifting to a new rule is a form of behavioral flexibility that is impaired in numerous psychiatric and neurological illnesses. Animal studies have revealed that this form of flexibility depends upon norepinephrine (NE) neurotransmission. Atomoxetine, a NE reuptake inhibitor, improves performance of humans in set shifting tasks. Our objective was to validate its effects in a rodent set shifting task. We tested the drug effect using an operant task that required a shift from a visual cue-guided behavior to a novel location-guided rule. A 1.0-mg/kg dose significantly accelerated rule shifting without affecting learning strategies, such as win-stay or lose-shift. Fitting behavioral performance with a learning function provided a measure of learning rate. This novel analysis revealed that atomoxetine accelerated shifting to the new rule without affecting learning rate.
    Psychopharmacology 07/2015; 232(20). DOI:10.1007/s00213-015-4028-5 · 3.88 Impact Factor
    • "Reversal learning as measured in the reversal phases of the CANTAB ID/ED-task of executive functioning is sensitive to deficits in patients with schizophrenia, independently of generalised intelligence (Leeson et al. 2009). These reversal learning deficits likely represent underlying abnormalities in fronto-striatal circuits, as these structures have been linked to reversal learning through imaging studies in humans (O'Doherty et al. 2003) as well as through excitotoxic and neurotransmitter-selective lesion studies in experimental animals (Bussey et al. 1997a, b; Schoenbaum et al. 2002; McAlonan and Brown 2003; Chudasama and Robbins 2003; Kim and Ragozzino 2005; Bissonette et al. 2008; Ghods- Sharifi et al. 2008; Burke et al. 2009; Graybeal et al. 2011). Specifically, intact 5-HT signalling in the orbitofrontal cortex (OFC) and dopamine signalling in the caudate nucleus (primates) or dorsomedial striatum (rodents) is critical for successful reversal learning (Clarke et al. 2004, 2011; O'Neill and Brown 2007; Boulougouris and Robbins 2010; Groman et al. 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.
    Psychopharmacology 07/2015; DOI:10.1007/s00213-015-4007-x · 3.88 Impact Factor
  • Source
    • "One notable finding in our study was the overall lack of impairment in rats following the OFC and NAc disconnections. Several studies have indicated that these two structures contribute to decision-making by encoding or updating the value of expected rewards (Schoenbaum et al., 2002; Izquierdo et al., 2004; Roesch & Olson, 2004; Kable & Glimcher, 2007; Roesch et al., 2009) and both structures are sensitive to the effects of reward uncertainty (Cardinal et al., 2001; Kheramin et al., 2002; Mobini et al., 2002; Abela & Chudasama, 2013; Stopper et al., 2014; but see St Onge & Floresco , 2010). Our OFC/NAc disconnection did not cause any changes in choice behavior for this type of decision, suggesting that, although both of these structures may independently contribute to such decisions, their intrahemispheric interaction is not critical. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Human cognition depends upon the capacity to make decisions in the present that bear upon outcomes in the future. The nucleus accumbens, a recipient of direct projections from both the hippocampus and orbitofrontal cortex, is known to contribute to these aspects of decision-making. Here we demonstrate that interaction of the nucleus accumbens with the hippocampus, but not the orbitofrontal cortex, is critical in shaping decisions that involve time trade-offs. Compared with controls, rats with a disrupted hippocampal-accumbens interaction were strongly biased toward choosing stimuli that led to small and immediate food rewards over large and delayed ones. We show that this pattern of behavior cannot be ascribed to impaired representation of stimulus value, the incapacity to wait, or a general disruption of decision-making. These results identify a hippocampal-accumbens circuit that may underlie a range of problems in which daily decisions are marked by a shift toward immediate gratification. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Neuroscience 06/2015; 42(5). DOI:10.1111/ejn.13009 · 3.18 Impact Factor
Show more