The effects of juvenile stress on anxiety, cognitive bias and decision making in adulthood:a rat model

Stress experienced in childhood is associated with an increased risk of developing psychiatric disorders in adulthood. These disorders are particularly characterized by disturbances to emotional and cognitive processes, which are not currently fully modeled in animals. Assays of cognitive bias have recently been used with animals to give an indication of their emotional/cognitive state. We used a cognitive bias test, alongside a traditional measure of anxiety (elevated plus maze), to investigate the effects of juvenile stress (JS) on adulthood behaviour using a rodent model. During the cognitive bias test, animals were trained to discriminate between two reward bowls based on a stimulus (rough/smooth sandpaper) encountered before they reached the bowls. One stimulus (e.g. rough) was associated with a lower value reward than the other (e.g. smooth). Once rats were trained, their cognitive bias was explored through the presentation of an ambiguous stimulus (intermediate grade sandpaper): a rat was classed as optimistic if it chose the bowl ordinarily associated with the high value reward. JS animals were lighter than controls, exhibited increased anxiety-like behaviour in the elevated plus maze and were more optimistic in the cognitive bias test. This increased optimism may represent an optimal foraging strategy for these underweight animals. JS animals were also faster than controls to make a decision when presented with an ambiguous stimulus, suggesting altered decision making. These results demonstrate that stress in the juvenile phase can increase anxiety-like behaviour and alter cognitive bias and decision making in adulthood in a rat model

The differential impact of social defeat on mice living in isolation or groups in an enriched environment: Plasma corticosterone and monoamine variations

Social defeat in mice is a potent stressor that promotes the development of depressive- and anxiety-like behaviours, as well as variations of neuroendocrine and brain neurotransmitter activity. Although environmental enrichment may protect against some of the adverse behavioural and biological effects of social defeat, it seems that, among male group-housed mice maintained in an enriched environment (EE), aggressive behaviours may be more readily instigated, thus promoting distress and exacerbating psychopathological features. Thus, although an EE can potentially have numerous beneficial effects, these may depend on the general conditions in which mice were raised. It was observed in the current investigations that EE group-housed BALB/cByJ mice displayed increased anxiety-like behaviours compared to their counterparts maintained in a standard environment (SE). Furthermore, in response to social defeat, EE group-housed male mice exhibited decreased weight gain, exaggerated corticosterone elevations and altered hippocampal norepinephrine utilization compared to their SE counterparts. These effects were not apparent in the individually housed EE mice and, in fact, enrichment among these mice appeared to buffer against serotonin changes induced by social defeat. It is possible that some potentially beneficial effects of enrichment were precluded among group-housed mice, possibly owing to social disturbances that might occur in these conditions. In fact, even if social interaction is an essential feature of enrichment, it seems that some of the positive effects of this housing condition might be optimal when mice are housed individually, particularly with regard to buffering the effects of social defeat

Assessment of MRI scanner performance for preclinical functional studies

Functional Magnetic Resonance Imaging (fMRI) based studies are rapidly expanding in the field of preclinical research. The majority of these studies use Echo Planar Imaging (EPI) to measure Blood Oxygenation Level Dependent (BOLD) signal contrasts in the brain. In such studies the magnitude and statistical significances of these contrasts are then related to brain function and cognition. It is assumed that any observed signal contrast is ultimately due to differences in biological state and that scanner performance is stable and repeatable between subjects and studies. However, due to confounding issues introduced by in vivo subjects, little work has been undertaken to test this basic assumption. As the BOLD signal contrasts generated in such experiments are often very low, even small changes in scanner performance may dominate the BOLD contrast, distorting any biological conclusions drawn. A series of fMRI phantoms were produced to measure scanner performance independent of biological subjects. These phantoms produce specified signal contrast levels on demand during an fMRI scan by means of current-induced magnetic field gradients. These were used to generate data sets that emulated the BOLD signal contrast of in vivo imaging. Two studies examining scanner performance were then conducted on high-field preclinical MRI scanners. Firstly, in a longitudinal study on a single scanner, measurements were taken over a number of days across a week long period and then every two months over a year long period. Secondly, the behaviour of four preclinical scanners (three at 7T, one at 9.4T) was comparatively assessed. Measurements of several imaging parameters including contrast generated and functional contrast to noise ratio (fCNR) were obtained in both studies. If the scanners involved are truly comparable then they should generate similar measurement values. Across both studies parameter measurements showed significant differences for identical contrast settings on the phantom. Although signal contrast itself proved very comparable across the studies fCNR proved to be highly variable. As well as these measurements of longer tem behaviour proving variable, short and mid-term signal stability displayed a wide range of variability. Variations in the level and quality of both signal and noise were observed. Modelling of signal changes based on fundamental physical principles was also performed for comparison. The impact of these behaviours and variations on in vivo studies could result in skewed biological conclusions at any single site, with some sites exhibiting greater problems than others. The multisite results suggest potential difficulties when comparing biological conclusions between sites, even when using identical imaging parameters. In summary, these results suggest that a cautious approach should be taken with the conclusions of both fMRI and associated resting state connectivity studies that use EPI as their acquisition sequence. Improvements to both the experimental design of studies and regular quality monitoring of scanners should be undertaken to minimise these effects. Clinical MRI scanners should also be assessed for similar aberrations in behaviour

Stressor exposure of male and female juvenile mice influences later responses to stressors: Modulation of GABA A receptor subunit mRNA expression

Stressors encountered during the juvenile period may have persistent effects on later behavioral and neurochemical functioning and may influence later responses to stressors. In the current investigation, we evaluated the influence of stressor exposure applied during the juvenile period (26-28days of age) on anxiety-related behavior, plasma corticosterone and on GABA A α2, α3, α5 and γ2 mRNA expression within the prefrontal cortex (PFC) and amygdala measured during adulthood. These changes were monitored in the absence of a further challenge, as well as in response to either a social or a non-social psychogenic stressor administered during adulthood. Exposure to an acute adult stressor elicited anxiety in females and was still more pronounced among females that had also experienced the juvenile stressor. Among males, arousal and impulsivity predominated so that anxiety responses were less notable. Furthermore, experiencing the stressor as a juvenile influenced adult GABA A subunit expression, as did the adult stressor experience. These changes were differentially expressed in males and females. Moreover, these subunit variations were further moderated among mice that stressed as juveniles and were again exposed to an adult stressor. Interestingly, under conditions in which the juvenile stressor increased the expression of a particular subunit, exposure to a further stressor in adulthood resulted in the γ-aminobutyric acid (GABA) subunit variations being attenuated in both sexes. The current results suggest that juvenile and adult stressor experiences elicit variations of GABA A receptor subunit expression that are region-specific as well as sexually-dimorphic. Stressful even

Incarnation and animation: physical versus representational deficits of body integrity

Two apparently disparate phenomena of defective body integrity are reviewed. The first concerns dysmelia, characterized by the congenital absence or deformation of limbs, and the focus of the review is on phantom sensations of people with this kind of physical integrity disorder. The second phenomenon consists of non-psychotic individuals' desire to have a healthy limb amputated, which is interpreted as a mismatch between the physical integrity of a particular limb and its representation in multimodal cortical areas of the brain. We outlined commonalities and differences between the two conditions and note the absence, in both areas of research, of a unified theory that would account for the reported phenomenology. Phantom limbs in dysmelia and the desire for limb amputation most likely are the consequence of very early developmental dissociations between physical and phenomenal body shapes. They are mirror images of one another in that the former constitutes an "animation without incarnation" and, the latter, an "incarnation without animation"