Nichola M. Brydges

Environmental enrichment induces optimistic cognitive bias in rats

People’s affective or emotional state can alter their cognitive processing, biasing interpretation of ambiguous stimuli. Those in a more positive state interpret such stimuli in a more optimistic manner than those in a negative state. Recently this research has extended to animals, and has shown that manipulations associated with negative affect cause animals to interpret ambiguous stimuli more pessimistically. We investigated whether exposure to environmental enrichment engenders optimistic responses to ambiguous stimuli. Rats, Rattus norvegicus, were trained on a novel conditional discrimination task whereby they learned the correct response necessary to obtain a food reward given the stimulus present during approach (rough or smooth sandpaper). One stimulus was associated with a higher-value reward than the other. Once the rats were trained, cognitive bias was probed by exploring their responses to an ambiguous stimulus (intermediate grade of sandpaper); a rat was defined as optimistic if it chose the response appropriate to the stimulus associated with the better reward. Animals transferred from unenriched to enriched cages showed more optimistic responses following the change. A control group maintained in unenriched cages showed pessimistic responses throughout. These results demonstrate for the first time that environmental enrichment can induce an optimistic cognitive bias in rats previously housed in standard caging, possibly indicative of a more positive affective state. These results add support to the suggestion that measuring cognitive biases can give an insight into animal emotional states; this has implications for animal welfare and preclinical testing of potential therapeutics for mood disorders.

Habitat stability and predation pressure affect temperament behaviours in populations of three‐spined sticklebacks

1. There is growing interest in the causes and consequences of animal temperaments. Temperament behaviours often have heritable components, but ecological variables can also affect them. Numerous variables are likely to differ between habitats, and these may interact to influence temperament behaviours. 2. Temperament behaviours may be correlated within populations (behavioural syndromes), although the underlying causes of such correlations are currently unclear. 3. We analysed three different temperament behaviours and learning ability in three-spined sticklebacks, Gasterosteus aculeatus, to determine how different ecological variables influence them both within and between populations. We selected populations from four ponds and four rivers that varied naturally in their exposure to predators. 4. High-predation river populations were significantly less bold than a high-predation pond and low-predation river populations, and low-predation pond populations were significantly less bold than a high-predation pond population. Within populations, temperament behaviours were correlated in one high-predation river population only. 5. These results suggest that multiple ecological factors can interact to affect temperament behaviours between populations, and also correlations in those behaviours within populations.

Habitat stability and predation pressure influence learning and memory in populations of three-spined sticklebacks

Learning and memory enable animals to adjust their behaviour in variable environments. Not all habitats vary to the same extent, and thus different environments can affect learning and memory in different ways. Habitat stability is one of numerous environmental variables proposed to influence what animals learn, but it is unlikely to act alone. To investigate how multiple variables affect learning and memory behaviour, we compared spatial learning and memory in three-spined sticklebacks from four ponds (stable habitat) and four rivers (unstable habitat) of varying predation pressure. Contrary to initial predictions, river fish had longer memory duration (>1 week) than pond fish (<1 week). Learning rate was affected by an interaction between habitat stability and predation pressure, with low-predation river populations learning faster than high-predation river populations. These results show that learning and memory can be affected in different ways by contrasting ecological factors and that multiple ecological factors can interact to shape learning and memory, thus emphasizing the importance of considering multiple ecological variables when investigating behaviour.

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.

Clinical assessments of increased sensory sensitivity in dogs with cranial cruciate ligament rupture

Dogs with chronic pain have a compromised quality of life. Repeatable and accurate sensory assessments form a means by which the hypersensitivity likely to reflect chronic pain may be quantified. These assessments can be applied to individuals to identify those that may benefit from improved analgesic relief. In this study four sensory assessments were evaluated in dogs presenting with a naturally occurring chronic painful condition (cranial cruciate ligament rupture, CCLR) and were compared with healthy control animals of similar age and weight. Inter-digital von Frey filament and thermal sensitivity tests revealed that the affected hind limb of dogs with CCLR was significantly more sensitive than the opposing limb. Static weight bearing and gait parameter scores were also reduced in the affected hind limb compared to the opposing hind limb of dogs with CCLR; no such differences were found between the hind limbs of healthy (control) dogs. The quantitative sensory tests permitted the differentiation of limbs affected by CCLR from healthy limbs. Dogs presenting with CCLR demonstrate objectively quantitative sensory sensitivities, which may require additional consideration in case management.

Imaging conditioned fear circuitry using awake rodent fMRI.

Functional magnetic resonance imaging (fMRI) is a powerful method for exploring emotional and cognitive brain responses in humans. However rodent fMRI has not previously been applied to the analysis of learned behaviour in awake animals, limiting its use as a translational tool. Here we have developed a novel paradigm for studying brain activation in awake rats responding to conditioned stimuli using fMRI. Using this method we show activation of the amygdala and related fear circuitry in response to a fear-conditioned stimulus and demonstrate that the magnitude of fear circuitry activation is increased following early life stress, a rodent model of affective disorders. This technique provides a new translatable method for testing environmental, genetic and pharmacological manipulations on emotional and cognitive processes in awake rodent models.

Juvenile stress enhances anxiety and alters corticosteroid receptor expression in adulthood

Exposure to stress in early life is correlated with the development of anxiety disorders in adulthood. The underlying mechanisms are not fully understood, but an imbalance in corticosteroid receptor (CR) expression in the limbic system, particularly the hippocampus, has been implicated in the etiology of anxiety disorders. However, little is known about how prepubertal stress in the so called “juvenile” period might alter the expression of these receptors.

Imaging learned fear circuitry in awake mice using fMRI

Functional magnetic resonance imaging (fMRI) of learned behaviour in ‘awake rodents’ provides the opportunity for translational preclinical studies into the influence of pharmacological and genetic manipulations on brain function. fMRI has recently been employed to investigate learned behaviour in awake rats. Here, this methodology is translated to mice, so that future fMRI studies may exploit the vast number of genetically modified mouse lines that are available. One group of mice was conditioned to associate a flashing light (conditioned stimulus, CS) with foot shock (PG; paired group), and another group of mice received foot shock and flashing light explicitly unpaired (UG; unpaired group). The blood oxygen level‐dependent signal (proxy for neuronal activation) in response to the CS was measured 24 h later in awake mice from the PG and UG using fMRI. The amygdala, implicated in fear processing, was activated to a greater degree in the PG than in the UG in response to the CS. Additionally, the nucleus accumbens was activated in the UG in response to the CS. Because the CS signalled an absence of foot shock in the UG, it is possible that this region is involved in processing the safety aspect of the CS. To conclude, the first use of fMRI to visualise brain activation in awake mice that are completing a learned emotional task is reported. This work paves the way for future preclinical fMRI studies to investigate genetic and environmental influences on brain function in transgenic mouse models of disease and aging.

Juvenile stress produces long-lasting changes in hippocampal DISC1, GSK3ß and NRG1 expression

Juvenile stress produces long-lasting changes in hippocampal DISC1, GSK3s and NRG1 expression

Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring

Abstract Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders.