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Alterations in behaviour can arise through a number of factors, including strain and sex. Here, we explored strain and sex differences between Long–Evans (LER) and Wistar (WR) male and female rats that had been trained in a myriad of behavioural tasks. Tests included those assessing motor learning (skilled reaching task), spatial learning and memory (Morris water task), contextual learning (discriminative fear-conditioning to context) and anxiety behaviour (elevated plus maze). Following behavioural assessment, associated brain areas were examined for volumetric differences, including the hippocampus and its subregions, prefrontal cortex areas and the amygdala. LER and WR differed in their rates of performance in the skilled reaching task throughout the training period. Overall, LER outperformed WR in tasks related to contextual and spatial learning, although this was not accompanied by larger volumes of associated brain areas. Males outperformed females in spatial learning, and females outperformed males in the contextual fear-conditioning task and had an associated larger amygdalar volume, although these sexual dimorphisms were only observed within the LER strain. Overall, this study highlights differences between these two rat strains as well as highlights that larger volumetric estimates of brain areas do not always confer improved function of associated behaviours. [ABSTRACT FROM AUTHOR]

Abstract: The influences of complex housing, T-maze, and Grice box training on dendritic morphology of the prefrontal cortex (PFC) and primary somatosensory (Par 1) were investigated in the rat. Golgi–Cox analyses demonstrated that all learning paradigms produced alterations in PFC connectivity, albeit differently. Furthermore, the effects of experience on dendritic morphology varied by region, hemisphere, and lamina and often resulted in opposing changes within each. For example, complex housing produced a time-dependent decrease in the dendritic fields of layer (L) V neurons in region 3 of the cingulate cortex (Cg3) in the medial PFC (mPFC) neurons and increases in LIII of the dorsal agranular insular (AID) region of the orbitofrontal cortex. In contrast, T-maze training produced increases in Cg3 LV and decreases in AID LIII spine density. Of interest, the influence of experience was not reflected equally between hemispheres. For example, T-maze training produced an increase in Cg3 LV and AID LIII branch order and length in the right hemisphere, and an increase in Cg3 LIII branch order in the left hemisphere. Additionally, correlation analysis of task performance and dendritic morphology indicated an opposing influence of experience within the different laminae of the Cg3. For example, whereas, performance was negatively correlated with Cg3 LV dendritic branch order/length, there was a positive correlation with Cg3 LIII dendrites. Complex housing induced changes in the Par 1were also time -dependent but were only apparent after a prolonged period of exposure. In addition to demonstrating learning-specific modifications in dendritic connectivity within the PFC, the results illustrate varying patterns of change that likely reflect task-dependent requirements on the PFC. [Copyright &y& Elsevier]

Abstract: Our study focuses on the physiological effects of repetition on learning and working memory using an adaptation of Luria''s Memory Word-Task (LMWT). We assess the hemodynamic response in dorsolateral prefrontal cortex (DLPFC) of 13 healthy subjects while completing LMWT. Free word recalls were acquired at the beginning, middle and end of the task. Behavioral results showed that all subjects could recall the complete word list by the 10th trial, which was considered as successful task accomplishment. We observed an attenuation of stimulus-evoked neural activity in prefrontal neurons. Our findings show that the temporal integration of efficient verbal learning is mediated by a mechanism known as neural repetition suppression (NRS). This mechanism facilitates cortical deactivation in DLPFC once learning is successfully completed. This cortical reorganization is interpreted as a progressive optimization of neural responses to produce a more efficient use of neural circuits. NRS could be considered one of the natural mechanisms involved in the processes of memory learning. [Copyright &y& Elsevier]

Abstract: Several executive functions rely on the medial prefrontal cortex (mPFC) in the rat. Aspiration and neurotoxic lesions of the mPFC impair reversal learning in adult rats. Systemic administration of MK-801, an NMDA-receptor antagonist, impairs T-maze reversal learning in weanling rats but the role of mPFC NMDA-receptor antagonism in this effect is not known in either adult or young animals. This set of studies showed that mPFC NMDA receptors are specifically involved in T-maze discrimination reversal in weanling rats. In Experiment 1, 26-day-old rats (P26) demonstrated a dose-dependent impairment following bilateral mPFC administration of either 2.5 or 5.0μg MK-801 or saline (vehicle) during the reversal training phase only. In Experiment 2, P26 rats were trained on the same task, but four groups of rats received bilateral mPFC infusions during acquisition only (MK–SAL), reversal only (SAL–MK), both phases (MK–MK), or neither phase (SAL–SAL). MK-801 impaired performance only when infused during reversal. This suggests that NMDA-receptor antagonism in the mPFC is selectively involved in reversal learning during development and this may account for the previously reported effects of systemic MK-801 on T-maze discrimination reversal in weanling rats. [Copyright &y& Elsevier]

It has been demonstrated previously that lesions to medial prefrontal cortex in rats impair the shifting of attentional set between perceptual features of complex stimuli [J. Neurosci. 20 (2000) 4320], a result that mirrors the deficit found in humans and monkeys [Nature 380 (1996) 69; Behav. Neurosci. 110 (1996) 872; J. Neurosci. 17 (1997) 9285; Neuropsychologia 29 (1991) 993]. These data imply functional homology between rat medial prefrontal cortex and primate prefrontal cortex.In marmoset monkeys, there is a double dissociation between the effects of lesions of lateral prefrontal cortex, which impair shifting of attentional set, and lesions of orbital prefrontal cortex, which result in impairments of reversal of stimulus-reward contingencies, leaving attentional set-shifting capacities intact [Nature 380 (1996) 69; Behav. Neurosci. 110 (1996) 872; J. Neurosci. 17 (1997) 9285].The present investigation examined whether lesions to rat orbital prefrontal cortex would produce deficits in reversal learning in the absence of deficits in shifting attentional set, as seen in monkeys. Rats were trained to perform an attentional set-shifting task that is formally the same as that used in monkeys and humans. In a single session, rats performed a series of discriminations, including acquisitions and reversals. Damage to orbital prefrontal cortex in the rats did not disrupt the ability to acquire, maintain or shift attentional set. We report here the same selective impairment in reversal learning in rats as seen in primates with orbital prefrontal cortex lesions. [Copyright &y& Elsevier]

In order to test an attribute specificity model of prefrontal cortex function, rats with lesions in the prelimbic–infralimbic (PL–IL) or anterior cingulate and precentral (AC–PC) subregions of the medial prefrontal cortex and controls were trained on an object–place paired associate task. Rats with AC–PC lesions acquired the task as readily as controls. In contrast, the PL–IL lesioned rats did not learn the task. Whenever higher order processing is required to solve a task, the data support an attribute-specificity model of prefrontal cortex function in that the PL–IL cortices support both object and place attribute information in a variety of tasks including object–place paired associate learning. [Copyright &y& Elsevier]

Increasingly precise molecular genetic tools are available to study in mice the cellular mechanisms underlying complex brain functions, but the behavioural paradigms to assess these functions often lack the required specificity. In this study, an attentional set-shifting paradigm to assess medial frontal cortex functions in rats was modified for use in mice and variation between two relevant mouse strains assessed. Male 129/SvEv and C57BL/6J mice and their F1 intercross (n=8 per genotype) were trained to dig in bowls for a food reward. On four consecutive days, mice performed a series of discriminations to criterion (six consecutive correct choices) between pairs of food bowls that differed along two dimensions (odour, digging medium), including a reversal, an intra-dimensional shift, and an extra-dimensional shift. Mice from the 129 strain performed significantly better than C57 mice in the initial acquisition of a simple discrimination and in the final extra-dimensional shift test, with no difference in the reversal and intra-dimensional shift. Performance of the F1 mice was intermediate or similar to that of the 129 mice. These results indicate a selective difference between these two strains in attentional selection processes that have been shown in humans, monkeys and rats to be mediated by prefrontal cortex. [Copyright &y& Elsevier]