Do rats have a prefrontal cortex? Behav Brain Res

Netherlands Institute for Brain Research, KNAW, Graduate School Neurosciences, Meibergdreef 33, 1105 AZ, Amsterdam, The Netherlands.
Behavioural Brain Research (Impact Factor: 3.03). 12/2003; 146(1-2):3-17. DOI: 10.1016/j.bbr.2003.09.028
Source: PubMed


The lack of a single anatomical or functional definition of 'prefrontal cortex' has led to different and, in some respects, controversial views on the existence of a prefrontal cortex in non-primate mammals, in particular in rats. Until the classic paper by Rose and Woolsey [Res. Publ. Assoc. Nerv. Ment. Dis. 27 (1948) 210], the general idea was that a prefrontal cortex is unique to primate species. Rose and Woolsey's 'prefrontal cortex' definition was based upon a single anatomical criterion, i.e. the cortical projection area of the mediodorsal thalamic nucleus. Single criteria, however, do not appear to be sufficient for defining the prefrontal cortex. Therefore, other anatomical and functional characteristics are currently used to identify the prefrontal cortex in different species. Yet, recently the debate about the nature of the prefrontal cortex in non-primate species has been resumed. In the present paper we will compare the structural and functional characteristics of the prefrontal cortex of nonhuman primates and rats. We will argue that rats have a functionally divided prefrontal cortex that includes not only features of the medial and orbital areas in primates, but also some features of the primate dorsolateral prefrontal cortex.

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Available from: Harry Uylings, Oct 13, 2015
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    • "Therefore, the ACC may be required for subjects to learn the contingencies of winning and losing, but not the actual decision-making process, similar to the role of the OFC. The dlPFC of humans, homologous to the medial prefrontal cortex (mPFC) in rats (Uylings et al. 2003; Seamans et al. 2008), is largely involved in working memory (Ragozzino 2007). However, the human dlPFC and areas of the rat mPFC—specifically the prelimbic (PrL) and infralimbic (IL) sub-regions—may also be important in cost-benefit decisionmaking . "
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    ABSTRACT: Rationale: Studies employing the Iowa Gambling Task (IGT) demonstrated that areas of the frontal cortex, including the ventromedial prefrontal cortex, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex, and anterior cingulate cortex (ACC), are involved in the decision-making process. However, the precise role of these regions in maintaining optimal choice is not clear. Objectives: We used the rat gambling task (rGT), a rodent analogue of the IGT, to determine whether inactivation of or altered dopamine signalling within discrete cortical sub-regions disrupts decision-making. Methods: Following training on the rGT, animals were implanted with guide cannulae aimed at the prelimbic (PrL) or infralimbic (IL) cortices, the OFC, or the ACC. Prior to testing, rats received an infusion of saline or a combination of baclofen and muscimol (0.125 μg of each/side) to inactivate the region and an infusion of a dopamine D2 receptor antagonist (0, 0.1, 0.3, and 1.0 μg/side). Results: Rats tended to increase their choice of a disadvantageous option and decrease their choice of the optimal option following inactivation of either the IL or PrL cortex. In contrast, OFC or ACC inactivation did not affect decision-making. Infusion of a dopamine D2 receptor antagonist into any sub-region did not alter choice preference. Conclusions: Online activity of the IL or PrL cortex is important for maintaining an optimal decision-making strategy, but optimal performance on the rGT does not require frontal cortex dopamine D2 receptor activation. Additionally, these results demonstrate that the roles of different cortical regions in cost-benefit decision-making may be dissociated using the rGT.
    Psychopharmacology 09/2015; DOI:10.1007/s00213-015-4075-y · 3.88 Impact Factor
    • "Since the human PFC is much larger and more differentiated than that in the rat, in the present study we selected the DLPFC as a region of the human cortex that has been previously demonstrated as exhibiting aberrant functional connectivity with the hippocampus in disease and at-risk states (Esslinger et al. 2009; Meyer- Lindenberg et al. 2005). Since granular prefrontal cortex (including DLPFC) appeared during primate evolution, the rat brain lacks a granular cortex, thus making it difficult to confidently establish an area homologous the primate DLPFC (Preuss 1995; Uylings et al. 2003). The closest homolog of human DLPFC in rats is the PrL in terms of anatomical connections and electrophysiological and computational properties (Seamans et al. 2008). "
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    ABSTRACT: Aberrant prefrontal-hippocampal (PFC-HC) connectivity is disrupted in several psychiatric and at-risk conditions. Advances in rodent functional imaging have opened the possibility that this phenotype could serve as a translational imaging marker for psychiatric research. Recent evidence from functional magnetic resonance imaging (fMRI) studies has indicated an increase in PFC-HC coupling during working-memory tasks in both schizophrenic patients and at-risk populations, in contrast to a decrease in resting-state PFC-HC connectivity. Acute ketamine challenge is widely used in both humans and rats as a pharmacological model to study the mechanisms of N-methyl-D-aspartate (NMDA) receptor hypofunction in the context of psychiatric disorders. We aimed to establish whether acute ketamine challenge has consistent effects in rats and humans by investigating resting-state fMRI PFC-HC connectivity and thus to corroborate its potential utility as a translational probe. Twenty-four healthy human subjects (12 females, mean age 25 years) received intravenous doses of either saline (placebo) or ketamine (0.5 mg/kg body weight). Eighteen Sprague-Dawley male rats received either saline or ketamine (25 mg/kg). Resting-state fMRI measurements took place after injections, and the data were analyzed for PFC-HC functional connectivity. In both species, ketamine induced a robust increase in PFC-HC coupling, in contrast to findings in chronic schizophrenia. This translational comparison demonstrates a cross-species consistency in pharmacological effect and elucidates ketamine-induced alterations in PFC-HC coupling, a phenotype often disrupted in pathological conditions, which may give clue to understanding of psychiatric disorders and their onset, and help in the development of new treatments.
    Psychopharmacology 07/2015; DOI:10.1007/s00213-015-4022-y · 3.88 Impact Factor
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    • "During rotarod training, animals learn anticipatory stepping movements and whole-body posture adjustments (Buitrago et al., 2004; Farr et al., 2006; Rothwell et al., 2014). Although the precise connectivity and function of M2 cortex in various motor behaviors are areas of continuing research (Brecht, 2011; Schneider et al., 2014), current evidence suggests that task-related somatosensory and spatial information may be relayed to M2 cortex via its inputs from posterior sensory and association cortices (Hoover and Vertes, 2007; Reep and Corwin, 2009; Uylings et al., 2003). In addition, M2 electrical stimulation has been reported to evoke movements of various body parts in anesthetized animals and coordinated whole-body motion in freely moving animals (Neafsey et al., 1986; Tennant et al., 2011; Yeomans and Tehovnik, 1988). "
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    ABSTRACT: Motor behaviors recruit task-specific neuronal ensembles in motor cortices, which are consolidated over subsequent learning. However, little is known about the molecules that can identify the participating neurons and predict the outcomes of the consolidation process. Using a mouse rotarod-learning task, we showed that lesion or inactivation of the secondary motor (M2) cortex disrupts learning of skilled movements. We tracked the endogenous promoter activity of the neuronal activity-regulated gene Arc in individual M2 neurons during rotarod learning by in vivo two-photon imaging of a knockin reporter. We found that task training initially recruits Arc-promoter-activated neurons and then consolidates them into a specific ensemble exhibiting persistent reactivation of Arc-promoter. The intensity of a neuron's initial Arc-promoter activation predicts its reactivation probability and neurons with weak initial Arc-promoter activation are dismissed from the ensemble during subsequent training. Our findings demonstrate a task-specific Arc-dependent cellular consolidation process in M2 cortex during motor learning. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neuron 06/2015; 86(6). DOI:10.1016/j.neuron.2015.05.022 · 15.05 Impact Factor
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