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Farrowing crates prevent sows during lactation from moving freely and interacting unrestrictedly with their piglets. The aim of this study was to compare sows during lactation in a group-housing system (GH; n = 23) and sows in a conventional single-housing system (SH; n = 24) with regard to their maternal behaviour. GH sows were only fixed in their pens three days ante partum until one day post partum. For the remaining amount of time they were able to choose between their home pen and a shared running area. Piglets were able to leave their pens on day five post partum. Data were collected in four batches with six sows in each housing system. All sows were observed in week 2 and week 4 of lactation in six successive tests concerning their maternal behaviour. The sows’ reaction to piglet distress calls, separation from and reunion with their piglets was tested both in their home pens and in a test arena for a maximum of five minutes. The test arena (3.9 m × 3.7 m) provided a piglet nest in a corner. The sows were only able to hear and smell their piglets. In the piglet scream test in the home pen, GH sows were more responsive to piglet screaming than SH sows. GH sows showed more body movements towards their screaming piglets and aggressiveness towards the experimenter (p

Background For reasons of cost and ethical concerns, models of neurodegenerative disorders such as Huntington disease (HD) are currently being developed in farm animals, as an alternative to non-human primates. Developing reliable methods of testing cognitive function is essential to determining the usefulness of such models. Nevertheless, cognitive testing of farm animal species presents a unique set of challenges. The primary aims of this study were to develop and validate a mobile operant system suitable for high throughput cognitive testing of sheep. New method We designed a semi-automated testing system with the capability of presenting stimuli (visual, auditory) and reward at six spatial locations. Fourteen normal sheep were used to validate the system using a two-choice visual discrimination task. Four stages of training devised to acclimatise animals to the system are also presented. Results All sheep progressed rapidly through the training stages, over eight sessions. All sheep learned the 2CVDT and performed at least one reversal stage. The mean number of trials the sheep took to reach criterion in the first acquisition learning was 13.9 ± 1.5 and for the reversal learning was 19.1 ± 1.8. Comparison with existing method(s) This is the first mobile semi-automated operant system developed for testing cognitive function in sheep. Conclusions We have designed and validated an automated operant behavioural testing system suitable for high throughput cognitive testing in sheep and other medium-sized quadrupeds, such as pigs and dogs. Sheep performance in the two-choice visual discrimination task was very similar to that reported for non-human primates and strongly supports the use of farm animals as pre-clinical models for the study of neurodegenerative diseases.

Besides being recognized as a potential welfare indicator, play behaviour has long been considered to have immediate and/or long-term benefits. In particular, it has been suggested that in play animals learn to cope physically and emotionally with unexpected events. Given that the propensity to play varies greatly between conspecific individuals, such interindividual variability in playfulness may be associated with differences in the animals' future behaviour, a prediction that has rarely been tested. To investigate whether different levels of playfulness in juvenility indeed coincide with behavioural differences in later life, 30 female C57BL/6J mice were subjected to the following series of behavioural observations and tests: (1) quantification of juvenile play behaviour; (2) behavioural testing in paradigms that assess anxiety-like behaviour and exploratory locomotion in an unfamiliar environment; and (3) observation of spontaneous behaviour in the familiar home cage environment. Surprisingly, a high level of juvenile playfulness was predictive of high levels of state anxiety and low levels of exploratory locomotion in later life. While this relationship existed already in adolescence, it became even more prominent in adulthood. By contrast, no substantial differences between playful and less playful mice were found with respect to home cage behaviour. While these findings may reflect better coping abilities in novel and dangerous environments in those mice that played the most during juvenility, they may also argue for the existence of different types of mice. Thus, despite genetic homogeneity and identical housing environments, preferences for either local or global use of space were observed that indicate the emergence of individuality. Concerning animal welfare, our findings suggest that play may constitute a plausible welfare indicator at the population level, but is probably less meaningful for the individual.

Epidemiological studies have shown an association between vitamin D deficiency and cognitive impairment. However, there is a paucity of preclinical data showing that vitamin D deficiency is a causal factor for impaired cognitive processing. The aim of this study was to assess two cognitive tasks, the 5 choice-serial reaction task and the 5 choice-continuous performance task in adult vitamin D (AVD) deficient BALB/c mice. Ten-week old male and female BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We found sex-dependent impairments in attentional processing and showed that male AVD-deficient mice were less accurate, took longer to respond when making a correct choice and were more likely to make an omission, without a change in the motivation to collect reward. By contrast, female AVD-deficient mice had a reduced latency to collect reward, but no changes on any other measures compared to controls. Therefore, we have shown that in otherwise healthy adult mice, vitamin D deficiency led to mild cognitive impairment in male but not female mice and therefore this model will be useful for future investigations into unravelling the mechanism by which vitamin D affects the adult brain and cognitive function.

In this eighteenth (2016) Annual Review Issue of The Journal of Pathology, we present a collection of 19 invited review articles that cover different aspects of cellular and animal models of disease. These include genetically-engineered models, chemically-induced models, naturally-occurring models, and combinations thereof, with the focus on recent methodological and conceptual developments across a wide range of human diseases.

Kognitivna fleksibilnost pomeni zmožnost spremembe določenega, manj optimalnega, vzorca vedenja v spreminjajočih se razmerah. Ta zmožnost je izjemnega pomena za preživetje in je povezana z mnogimi psihiatričnimi motnjami. Za razumevanje in preučevanje kognitivne fleksibilnosti je bilo razvitih več vedenjskih testov. Za enega pomembnejših in bolj uporabljenih se je izkazal test reverznega učenja. Ta uporablja set različnih vizualnih dražljajev, ki so izmenično nagrajeni ali nenagrajeni. S pomočjo testa so že bile ugotovljene nekatere možganske regije, ki so povezane z nadzorom kognitivne fleksibilnosti. To so predvsem podregije prefrontalne skorje – orbitofrontalna skorja in medialna prefrontalna skorja ter tudi striatum in amigdala. V raziskavi smo zato želeli raziskati vlogo teh podregij in lokalno specifičnega serotoninskega delovanja na kognitivno fleksibilnost. Uporabili smo test reverznega učenja, implementiranega v na dotik občutljiv zaslon, ki je bil izveden na živalskih modelih – podganah. Izvedli smo lokalne farmakološke manipulacije določenih možganskih regij s pomočjo intrakranialnih mikroinfuzij GABAergičnih in glutamatergičnih agensov ter antagonistov serotoninskih receptorjev. Ugotovili smo, da obstaja funkcionalna disociacija med medialno in lateralno orbitofrontalno skorjo. Ti regiji nimata samo različne ampak celo nasprotno funkcijo pri reverznem učenju in nadzoru ter inhibiciji vedenjskih odzivov in naučenega vedenja. Medialna prefrontalna skorja je prav tako pomembna pri reverznem učenju. Specifično serotoninsko signaliziranje v prefrontalni skorji pa se v naši raziskavi ni izkazalo za ključno pri reverznem učenju, kar kliče po nadaljnjih raziskavah. Cognitive flexibility, the ability to change the pattern of behaviour in the face of changing environmental conditions, is crucial for survival and is thus associated with many psychiatric disorders. To asses and study cognitive flexibility in different species many tasks have been developed including reversal learning paradigms. Reversal learning paradigms use a set of different stimuli which are in turn rewarded or not rewarded. They have pointed out important brain regions for the control of cognitive flexibility. Prefrontal cortex and its subregions – orbitofrontal cortex and medial prefrontal cortex with connections to the striatum and amygdala are implicated in cognitive flexibility. Therefore, we wanted to explore the role of prefrontal cortex subregions and site-specific serotonin signalling in cognitive flexibility using touchscreen-based serial reversal behavioural paradigm in rat models. We performed local pharmacological manipulations using intracranial microinfusions of GABAergic and glutamatergic agents as well as serotonin receptor antagonists. The behavioural testing provided us with some important insights. We showed that there is a functional dissociation between medial and lateral orbitofrontal cortex, which not only seems to have separate, but also opposite functions and is important for the inhibition of responses and previously learned behaviour. The medial prefrontal cortex is also implicated in cognitive flexibility. However, specific serotonin signalling modulation failed to produce any significant results and thus needs some further investigation.

The quest to better understand the pathophysiology of Parkinson's disease (PD) and to find new therapies to provide greater relief to affected patients continues. The use of animal models of PD has been invaluable in the process. Here, we review, through a historical lens, some of the contribution of the 6-hydroxydopamine-lesioned rat and of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned nonhuman primate, in refining our understanding of PD and its treatment-related complications. We examine the mechanisms underlying the toxicity of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and then explore some of the advances at the molecular, pharmacological, electrophysiological and surgical levels made while experimenting on these animal models. We also discuss behavioural testing that can be performed with these animal models and highlight some of their limitations.

Backround Large animal models, such as the transgenic (tg) Huntington disease (HD) minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. Objective The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping minipigs transgenic for Huntington disease (tgHD) and whether tgHD minipigs reveal changes in this domain compared to wildtype (wt) minipigs. Methods While conducting behavioural testing, vocalisation incidence was documented for a cohort of 14 tgHD and 18 wt minipigs. Statistical analyses were performed using Fisher’s Exact Test for group comparisons and McNemar’s Test for intra-visit differences between tgHD and wt minipigs. Results Vocalisation can easily be documented during phenotyping assessments of minipigs. Differences in vocalisation frequency across behavioural conditions were detected between tgHD and wt minipigs. Influence of the genotype on vocalisation was detectable during a period of 1,5 years. Conclusion Vocalisation may be a viable marker for phenotyping minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation. Acknowledgement This study was funded by the CHDI foundation.

BACKGROUND Large animal models, such as the transgenic (tg) Huntington disease (HD) minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. OBJECTIVE The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping minipigs transgenic for Huntington's disease (tgHD) and whether tgHD minipigs reveal changes in this domain compared to wildtype (wt) minipigs. METHODS While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt minipigs. Statistical analyses were performed using Fisher's Exact Test for group comparisons and McNemar's Test for intra-visit differences between tgHD and wt minipigs. RESULTS Vocalisation can easily be documented during phenotyping assessments of minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. CONCLUSION Vocalisation may be a viable marker for phenotyping minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.

Individual variation in the reproductive performance of sows has the potential for greater negative impacts in loose-farrowing systems. Therefore, the ability to select gilts that will perform well would be a major advantage. This study investigated the behaviour of gilts during pre-pubertal tests and farrowing behaviour in conventional crates and PigSAFE (Piglet and Sow Alternative Farrowing Environment) pens. Gilts underwent two phases of behavioural testing. First, gilts were subjected to three individual human interaction and three startle object tests randomly allocated to test sessions over 3 days (i.e. gilts had either a human or startle test first). Three weeks later, gilts underwent three human interaction and three novel object tests, in their stable group of six. Gilts farrowed in individual PigSAFE pens or conventional crates and behaviour was observed for 8 h from the first piglet birth. Data were analysed using linear mixed models and Spearman's rank correlations. A novel finding was the effect of individual test order: gilts that had the human interaction or startle object test first behaved differently. The first test was different whichever test type, with a higher latency to interact with the object or human, and gilts experiencing the startle test first interacted more with the human in all three subsequent tests. Gilts farrowing in crates and pens showed differences in behaviour, most notably, a lower frequency of piglet-directed aggression was seen in pens (P

To describe the audiological journey of a group of infants with auditory neuropathy spectrum disorder (ANSD) following the fitting of hearing aids, and to investigate the potential benefits of including cortical auditory-evoked potentials (CAEPs) and a measure of functional auditory behaviour during early audiological management.Results from chart revision of estimated hearing threshold, early behavioural testing, parental observation, and functional auditory behaviour assessments were described, and compared to visual reinforcement audiometry (VRA) thresholds obtained at a mean corrected age of 10 months (SD 3). The relationship with CAEPs and functional performance was examined.The study included 12 infants diagnosed with ANSD and fitted with amplification.The estimated 4FA at a mean corrected age of four months (SD5) was within ± 10 dB of VRA results in 75% of infants when unaided and aided behavioural observation audiometry (BOA), together with unaided and aided parental observations was combined. Infants with a greater proportion of CAEPs present had higher PEACH scores.Delaying amplification until VRA results were available would have led to a significant period of auditory deprivation for infants in this study group. None of the assessments could accurately determine hearing thresholds when used in isolation, however when used in combination clinicians were able to obtain sufficient information to fit hearing aids early, and identify infants requiring closer monitoring.

The orexins are widely regarded potential therapeutic targets for a range of disorders of appetitive motivation, including obesity. The motivational activator theory, the first coherent account of the orexin system's role in appetitive motivation, predicts that orexin release motivates appetitive behaviour when the reinforcer is highly salient, available under a high unit-cost or when reward seeking is cue-driven. The present study tested the effect of intracerebroventricular (i.c.v.) administration of the highly potent and commercially available dual orexin receptor antagonist, TCS 1102, on self-administration and reinstatement of palatable food seeking in hungry and sated rats. TCS 1102 was also tested on FR1, FR5, FR10 and PR schedules. Orexin neuron activation was measured by c-Fos/orexin-A immunohistochemistry after cue-induced reinstatement, an extinction test, or a home-cage control. No effect of i.c.v. TCS 1102 was observed on self-administration at any fixed or progressive ratio schedule of reinforcement or reinstatement in hungry or sated rats. Although there was robust recruitment of orexin neurons during behavioural testing conditions, there was no specific activation of these neurons during cue-induced reinstatement when compared to extinction testing conditions. These results suggest that orexin antagonism may not be a useful therapeutic target for obesity as it does not appear to regulate food-seeking, and that the conditions determining orexin involvement as a motivational activator may be less clear than currently understood.

Key points To shed light on the controversial issue of how chronic immobilization affects cortical output, adult rats were subjected to intracortical microstimulation at different time-points during and after unilateral forelimb casting. After cast application, cortical hypoexcitability appeared bilateral, specific for forelimb area, but stronger in the contralateral-to-cast hemisphere. Cortical excitability progressively decreased over 30 days of immobilization and, after cast removal, steadily increased, but remained partial at 15 days. Cortical application of the GABAA-receptor antagonist bicuculline revealed an impairment of intracortical synaptic connectivity in the forelimb area during the cast period and for up to 15 days after cast removal. Rehabilitation using a rotarod performance protocol did not advance the normalization of normal forelimb map extension and enabled cortical output towards the distal forelimb only in sites that had maintained their excitability. Cortical hypoexcitability following immobilization is caused by reversible impairment of intracortical synaptic connectivity. This may suggest new approaches in conditions that require longterm limb immobilization. Abstract Experimental and clinical studies have attempted to evaluate the changes in cortical activity seen after immobilization-induced longterm sensorimotor restriction, although results remain controversial. We used intracortical microstimulation (ICMS), which provides topographic movement representations of the motor areas in both hemispheres with optimal spatial characterization, combined with behavioural testing to unravel the effects of limb immobilization on movement representations in the rat primary motor cortex (M1). Unilateral forelimb immobilization in rats was achieved by casting the entire limb and leaving the cast in place for 15 or 30 days. Changes in M1 were bilateral and specific for the forelimb area, but were stronger in the contralateral-to-cast hemisphere. The threshold current required to evoke forelimb movement increased progressively over the period in cast, whereas the forelimb area size decreased and the non-excitable area size increased. Casting resulted in a redistribution of proximal/distal movement representations: proximal forelimb representation increased, whereas distal representation decreased in size. ICMS after cast removal showed a reversal of changes, which remained partial at 15 days. Local application of the GABAA-antagonist bicuculline revealed the impairment of cortical synaptic connectivity in the forelimb area during the period of cast and for up to 15 days after cast removal. Six days of rehabilitation using a rotarod performance protocol after cast removal did not advance map size normalization in the contralateral-to-cast M1 and enabled the cortical output towards the distal forelimb only in sites that had maintained their excitability. These results are relevant to our understanding of adult M1 plasticity during and after sensorimotor deprivation, and to new approaches to conditions that require longterm limb immobilization.

The primary causative event in the development of prion diseases is the misfolding of the normal prion protein (PrPC) into an ensemble of altered conformers (herein collectively denoted as PrPSc) that accumulate in the brain. Prominent amongst currently unresolved key aspects underpinning prion disease pathogenesis is whether transmission and toxicity are sub-served by different molecular species of PrPSc, which may directly impact on the development of effective targeted treatments. The use of murine models of prion disease has been of fundamental importance for probing the relationship between hypothesised "neurotoxic" and "transmissible" PrPSc and the associated kinetic profiles of their production during disease evolution, but unfortunately consensus has not been achieved. Recent in vivo studies have led to formulation of the "two-phase" hypothesis, which postulates that there is first an exponential increase in transmitting PrPSc species followed by an abrupt transition to propagation of neurotoxic PrPSc species. Such observations however, appear inconsistent with previous in vivo murine studies employing detailed time-course behavioural testing, wherein evidence of neurotoxicity could be detected early in disease progression. This review analyses the contributions of in vivo murine models attempting to provide insights into the relationship between transmitting and neurotoxic PrPSc species and explores possible refinements to the "two-phase hypothesis", that better accommodate the available historical and recent evidence.

In mammals, weaning constitutes an important phase in the progression to adulthood. It comprises the termination of suckling and is characterized by several changes in the behaviour of both mother and offspring. Furthermore, numerous studies in rodents have shown that the time point of weaning shapes the behavioural profile of the young. Most of these studies, however, have focused on 'early weaning', while relatively little work has been done to study 'late weaning' effects. The aim of the present study was therefore to explore behavioural effects of 'late weaning', and furthermore to gain insights into modulating effects of weaning age on the consistency of behavioural expressions over time. In total, 25 male and 20 female C57BL/6J mice, weaned after three (W3) or four (W4) weeks of age, were subjected to a series of behavioural paradigms widely used to assess anxiety-like behaviour, exploratory locomotion, and nest building performance. Behavioural testing took place with the mice reaching an age of 20 weeks and was repeated eight weeks later to investigate the stability of behavioural expressions over time. At the group level, W4 mice behaved less anxious and more explorative than W3 animals in the Open Field and Novel Cage, while anxiety-like behaviour on the Elevated Plus Maze was modulated by a weaning-age-by-sex interaction. Furthermore, weaning age shaped the degree of behavioural stability over time in a sex-specific way. While W3 females and W4 males displayed a remarkable degree of behavioural stability over time, no such patterns were observed in W3 males and W4 females. Adding to the existing literature, we could thus confirm that effects of weaning age do indeed exist when prolonging this phase, and were furthermore able to provide first evidence for the impact of weaning age and sex on the consistency of behavioural expressions over time.

Contains fulltext : 167237.pdf (Publisher’s version ) (Closed access) 'Big Data' and 'Population Imaging' are becoming integral parts of inspiring research aimed at delineating the biological underpinnings of psychiatric disorders. The scientific strategies currently associated with big data and population imaging are typically embedded in so-called discovery science, thereby pointing to the hypothesis-generating rather than hypothesis-testing nature of discovery science. In this issue, Yihong Zhao and F. Xavier Castellanos provide a compelling overview of strategies for discovery science aimed at progressing our understanding of neuropsychiatric disorders. In particular, they focus on efforts in genetic and neuroimaging research, which, together with extended behavioural testing, form the main pillars of psychopathology research.

The present study investigated the effect of upper limb skilled reach training in the intracerebral haemorrhage (ICH) model of rats.Forty-five male Sprague-Dawley rats with body weights of 200-250 g were divided randomly into the control (CON), ipsilateral (IST) and contralateral (CST) groups. All groups had induced ICH injury and were then rested to recover. Skilled reach training was applied on the left anterior paw in the ISP group and on the right paw in the CST group for 4 weeks. Behavioural testing, immunohistochemistry, western blotting and histological analysis were performed to confirm the expressions of neurotrophic factors and apoptosis-related proteins and brain recovery in the ICH rat model.The increased neurotrophic factors expression in the IST and CST groups decreased the expressions of Bax and Caspase-3, which was enhanced by CST. Moreover, decreased ischemic volume and progressive neurobehavioural outcome were observed in both the IST and CST groups.Skilled reach training promotes brain recovery and motor function through an increase of neurotrophic factors expression and a decrease of apoptosis-related protein expression.

a b s t r a c t The aim of the present paper was to examine in field conditions the feasibility of the exper- imentally developed behavioural tests for assessment of two temperamental traits of cold blood horses: fearfulness and reactivity to humans. The predictive, convergent and dis- criminant validity of the tests was evaluated. Fifty-three Polish Cold Blood Horses (CBHs) were tested with the battery of behavioural tests involving passive and active contact with humans, handling, startling, novel object and surface tests. The behaviour of horses in real, on-farm conditions was evaluated with the caretaker's questionnaire (CQ). The tests demonstrated that a non-startling object and unforced human manipulations were willingly accepted by horses. In contrast, the horses were more reluctant to interact spontaneously with humans and showed longer persistence of a withdrawal reaction when presented with a startling stimulus or when restrained. CQ confirmed the common opinion of calmness, patience and good manageability of the CBHs. The results of behavioural tests were correlated with the scores derived from factor anal- ysis of the CQ. Moreover, the majority of tests measures were correlated within reactivity to humans (median rs = 0.56) and fear tests (median rs = 0.41). Thus, predictive and con- vergent validity of the employed tests has been confirmed. However, reactivity to humans and fear measures were also correlated (median rs = 0.36), therefore discriminant validity of the tests used has been not confirmed. Therefore, we suggest that the parameters of tests designed to measure two separate traits: reactivity to humans and fearfulness, measured in fact avoidance of potential harm and withdrawal behaviour. Although selection for the work-appropriate behaviour is almost nonexistent nowadays, we conclude that Polish Cold Blood Horses are still predisposed for disciplines of equi- tation and driving, which demand an easy to handle horse. Nonetheless, we recommend behavioural testing of horses when approving for breeding. For this purpose, we can confirm usefulness of the experimentally developed tests in field assessment of general behavioural reactivity of horses.

Background Chronic Suppurative otitis media (CSOM) is a serious disorder particularly in low resource settings It can lead to disabling hearing impairment and sometimes life-threatening infective complications. Objective The aim of the present Study was to describe the characteristics of hearing impairment associated with CSOM in Yemeni children Methods. A case-control study of 75 children with CSOM and 74 healthy controls. Hearing was assessed by behavioural testing and audiometry Results: Cases had lower academic performance than controls (OR 15 31, 95% CI 1 99-322.14, p 30 dB was present in 51 5% (right ear) and 66.7% (left ear) of children with CSOM Conclusion: Disabling hearing impairment was identified as a major health problem in these Yemeni children with CSOM There is a need for investment to reduce the burden of CSOM and its complications in these communities. Greater attention to the chronic disabling effects of CSOM in children is required in poor communities and low resource settings (C) 2009 Elsevier Ireland Ltd All rights reserved

Purpose: Grating acuity values obtained with preferential looking techniques do not correspond to test results obtained with letter charts. The aim of the study was to investigate the agreement between grating acuity and other acuity tests. Methodc Twenty-eight adult patients with strabismic amblyopia were assessed with the preferential looking-method and other linear and single letter and symbol tests. Results: Assessment with preferential looking regularly led to an overestimation of the acuity values, but between preferential looking and single optotypes there was a much better agreement. This is most likely due to ‘crowding’ in strabismic amblyopia. A crowding ratio was calculated in the amblyopic eye, and crowding was found to be more prominent for comparisons of preferential looking with optotypes in rows, than for preferential looking and single optotypes. Conclusions: Strabismic amblyopia cannot be reliably identified with grating acuity. Preferential looking-testing is therefore of limited use as a screening method for the detection of amblyopia, but preferential looking could still be useful in the assessment and treatment.

The application of neuroscience advances to brain injury is addressed in the context of our studies of the role of the corpus callosum in the interhemispheric transfer of auditory and tactile information. The outcome of these studies, which were conducted over a period of 30 years in normal individuals as well as those with congenital and acquired lesions of the corpus callosum, have since been confirmed and extended by modern brain imaging techniques. These techniques nevertheless continue to rely on the use of sensitive, specific, valid and reliable behavioural testing paradigms.

Long-term potentiation (LTP) and depression (LTD) at parallel fibre-Purkinje cell synapses have been described in vitro in the cerebellar cortex, but the physiological roles of these two forms of plasticity have not been well defined. Here we show that, in cerebellar slices taken from rats that had undergone fear conditioning, there was a significant occlusion of electrically induced LTP at parallel fibre-Purkinje cell synapses. This effect was long-lasting and related to associative processes, as LTP was not occluded in unpaired animals. Notably, in conditioned animals the LTP-inducing protocol produced LTD in some cells instead of LTP. Conversely, synaptic depression induced by conjunctive stimulation of parallel fibers and climbing fibres was impaired in tissue taken immediately following aversive stimulation in both paired and unpaired subjects. This effect was not, however, long-lasting as the incidence and extent of LTD returned to normal levels 24 h after behavioural testing. These findings suggest that LTP takes part in the mechanisms underlying aversive associative memories in the cerebellum.

Objectives: We sought to determine whether rotenone, a commonly used pesticide, exhibits neurotoxicity in zebrafish by causing dopamine neuron loss through rotenone-induced oxidative damage. Methods: We exposed transgenic zebrafish embryos expressing green fluorescent protein under the control of the cis-regulatory elements of dopamine transporter (dat) to rotenone to determine the neurotoxic effects of rotenone on dopamine neuron abundance and pattern distribution, as well as the presence of apoptotic markers. The oxidative stress potential of rotenone on embryos was assessed using a live MitoSOX Red assay, and behavioural testing on adult zebrafish was assessed using video recordings of midline crossing events. Results: Zebrafish embryos treated with rotenone displayed a 50% reduction in dopamine neurons in the ventral diencephalon when exposed to 30µM rotenone (n=6, p

A functional MRI-naming paradigm was employed to investigate the neural correlates of successful phonological treatment in an individual with impaired word-retrieval poststroke. Items to be treated were selected in a pretest. A subsequent pretreatment fMRI scan measured brain activity during unsuccessful naming of objects to be treated and during successful naming of a comparison set of items. A phonological naming treatment was delivered 2 to 3 times weekly over 3 weeks with posttreatment behavioural testing indicating 100% accuracy on treated items. A posttreatment fMRI scan indicated that compared to the pretreatment scan, successful naming of treated items was associated with significantly increased brain activity in a number of left and right hemisphere regions including the left inferior parietal cortex which has been associated with phonological processing in healthy individuals, suggesting a candidate neural mechanism for sound-based treatments of naming.

As a consequence of their living close to humans as pets, for working purposes or as laboratory animals, dogs give evidence of behavioural variability, stemming from their innate capacities as well as from environmental influences. This paper reviews the behavioural tests used for dogs—tests which serve as an evaluation tool and those which serve as a means of classifying individual animals. In search of a consensus and standardisation, some material and methodological aspects of behavioural testing in dogs were collected. Behavioural test parameters that were taken into account were the terminology of the temperament concept, the test quality requirements and their implementation in the literature, the characteristics of the dog tested (source, breed, age, sex), the characteristics of the social and environmental stimuli used to elicit canine behaviour, the characteristics of the behavioural variables collected and the characteristics of the physical and physiological concomitant data obtained while assessing the behaviour. This review brings to light a lack of consensus regarding all these parameters. The procedures of testing are often particular to the investigator and thus unique. We emphasised this statement by comparing six research studies using a ball, carried out over 40 years. In view of all these differences in methodology, standardisation is suggested through the creation of a reference manual.

This study examined the influence of having a human resource (HR) manager in a small organization (less than 500 employees) in terms of the types of HR practices that are employed. Results indicated those organizations with no HR manager were less likely to utilize effective interviewing techniques, link pay to performance, or have formal training in place, when compared to those that did have an HR manager. There were no differences between the groups in terms of use of paper and pencil or behavioural testing for selection. Implications of these findings for small organizations and future research in this area are discussed.

ATP released from damaged or inflamed tissues can act at P2X receptors expressed on primary afferent neurones. The resulting depolarization can initiate action potentials that are interpreted centrally as pain. P2X3 subunits are found in a subset of small-diameter, primary afferent neurones, some of which are also sensitive to capsaicin. They can form homo-oligomeric channels, or they can assemble with P2X2 subunits into hetero-oligomers. Studies with antagonists selective for P2X3-containing receptors, experiments with antisense oligonucleotides to reduce P2X3 subunit levels, and behavioural testing of P2X3 knock-out mice, all suggest a role for the P2X2/3 receptor in the signalling of chronic inflammatory pain and some features of neuropathic pain. The availability of such tools and experimental approaches promises to accelerate our understanding of the other physiological roles for P2X receptors on primary afferent neurones.

Systems’ welfare evaluation, including behavioural testing, is becoming increasingly popular in farm animal assurance schemes. The aims of this study were to investigate whether fairly short-term exposure to gestation housing systems, which varied in physical, environmental and human-input factors, influenced behavioural and physiological measures during a human approach test—often used to identify problems in human–animal interactions. Twenty-four Large White×Landrace gilts were initially subjected to identical human contact and daily husbandry. Forty-two days after service, the gilts were randomly assigned to either an indoor housing system (n=16) or an outdoor housing system (n=8), which differed physically and in the amount of human contact and daily husbandry. The indoor system used an electronic sow feeder (ESF), was more space-limited and thermally-controlled and had human contact centered on cleaning out. The outdoor system was more extensive, had much greater space accessible, was not thermally-controlled and had human contact that centered around feeding. The human approach test was carried out on all gilts 30–44 days after entry to the gestation system. At testing, each individual was fitted with heart rate monitor and then moved into a test arena. After 2 min an unfamiliar human entered the pen and stood motionless for 3 min against one wall and then approached the gilt and touched her snout. Throughout the experimental period, behaviour and sound within the test arena were recorded continuously. During the 2 min familiarisation period, outdoor gilts had lower heart rates (108.2 bpm versus 123.7 bpm, P

Pain and allodynia following spinal cord injury are poorly understood and difficult to treat. Since there is evidence that supraspinal mechanisms are important in such pain, we have studied the role of the thalamus in an experimental model of spinal injury. Extracellular recordings were obtained from neurones of the thalamic nucleus ventralis postero-lateralis (VPL) in normal rats and those which had sustained a contusive spinal cord injury to the thoraco-lumbar junction 7 days previously. Behavioural testing with von Frey hairs established that 11 spinally injured rats showed exaggerated vocal responses to normally innocuous mechanical stimulation (allodynia) whereas eight were non-allodynic. Thalamic VPL neurones in spinally injured rats (both allodynic and non-allodynic) exhibited a dysrhythmia in that a significantly higher proportion fired spontaneously in an oscillatory mode when compared with neurones in uninjured rats. Thus this dysrhythmia was linked to spinal injury, not to allodynia. The evoked responses of VPL thalamic neurones to brushing the skin, however, were significantly elevated in allodynic rats when compared with those in uninjured rats and neuronal afterdischarges to these stimuli (which were absent in uninjured rats) were more common in allodynic than in non-allodynic rats. We have previously reported that a proportion of spinal neurones in allodynic spinally injured rats show increased evoked responses and afterdischarges following brushing the skin and hence the enhanced thalamic responses may reflect a greater spinal input. In view of the increasing evidence that thalamo-cortical rhythmical firing is linked to sensorimotor and cognitive brain functions, we propose that pain following brushing the skin results from an exaggerated spinal input being processed by a dysrhythmic thalamus. Thus both spinal and thalamic mechanisms may be important in the genesis of pain and allodynia following spinal cord injury.

Early symptomatic treatment of acute unilateral vestibulopathy is thought to impede the course of ensuing central vestibular compensation (VC). Despite the great clinical importance of this hypothesis there is no experimental evidence of its validity. The present study addressed this question by investigating the direct effect of 4-aminopyridine (4-AP) on ocular motor and postural symptoms in acute unilateral vestibulopathy as well as its long-term consequences for VC in a rat model of chemical unilateral labyrinthectomy (UL). After UL, one group of Sprague-Dawley rats was treated with 4-AP p.o. (1mg/kg/day), another with 0.9% NaCl solution p.o. for 3days. Behavioural testing for symptoms of vestibular tone imbalance was done 1day before and 1, 2, 3, 5, 7, 9, 15, 21, and 30days after UL. In addition, sequential whole-brain [(18)F]-FDG-μPET was performed before and 1, 3, 7, 15, and 30days after UL to examine and visualize 4-AP-induced modulation of VC. Administration of 4-AP on days 1-3 significantly improved postural imbalance 2h after administration compared to that in controls. This effect was only transient. Remarkably, the 4-AP group had a prolonged and impaired course of postural compensation compared to that of controls. The μPET revealed a significant increase of regional cerebral glucose metabolism (rCGM) in the vestibulocerebellum 2h after administration of 4-AP. However, the 4-AP group exhibited a persistent asymmetry of rCGM after day 3 in the vestibular nuclei and posterolateral thalami. In conclusion, this study confirms the hypothesis that early pharmacological abatement of vestibular symptoms impedes VC.

Birth is a particularly vulnerable time for acquiring brain injury. Unfortunately, very few treatments are available for those affected. Here we explore the effectiveness of prenatal intervention in an animal model of early brain damage. We used a complex housing paradigm as a form of prenatal enrichment. Six nulliparous dams and one male rat were placed in complex housing (condomom group) for 12 hours per day until the dams' delivered their pups. At parturition the dams were left in their home (standard) cages with their pups. Four dams were housed in standard cages (cagemom group) throughout pregnancy and with their pups until weaning. At postnatal day 3 (P3) infants of both groups received frontal cortex removals or sham surgery. Behavioural testing began on P60 and included the Morris water task and a skilled reaching task. Brains were processed for Golgi analyses. Complex housing of the mother had a significant effect on the behaviour of their pups. Control animals from the condomom group outperformed those of the cagemom group in the water task. Condomom animals with lesions performed better than their cagemom cohorts in both the water task and in skilled reaching. Condomom animals showed an increase in cortical thickness at anterior planes and thalamic area at both anterior and posterior regions. Golgi analyses revealed an increase in spine density. These results suggest that prenatal enrichment alters brain organization in manner that is prophylactic for perinatal brain injury. This result could have significant implications for the prenatal management of infants expected to be at risk for difficult birth.

Item does not contain fulltext The establishment of robust and replicable behavioural testing paradigms with translational value for psychiatric diseases is a major step forward in developing and testing etiology-directed treatment for these complex disorders. Based on the existing literature, we have generated an inventory of applied rodent behavioural testing paradigms relevant to autism spectrum disorders (ASD). This inventory focused on previously used paradigms that assess behavioural domains that are affected in ASD, such as social interaction, social communication, repetitive behaviours and behavioural inflexibility, cognition as well as anxiety behaviour. A wide range of behavioural testing paradigms for rodents were identified. However, the level of face and construct validity is highly variable. The predictive validity of these paradigms is unknown, as etiology-directed treatments for ASD are currently not on the market. To optimise these studies, future efforts should address aspects of reproducibility and take into account data about the neurodevelopmental underpinnings and trajectory of ASD. In addition, with the increasing knowledge of processes underlying ASD, such as sensory information processes and synaptic plasticity, phenotyping efforts should include multi-level automated analysis of, for example, representative task-related behavioural and electrophysiological read-outs.

The Nottingham Paediatric Cochlear Implant Programme (NPCIP) specializes in the implantation of children under 5 years of age. Subsequent tuning of the device and identification of changes in device function for these young children, who may have additional disabilities, can often be challenging. Thus, an objective measure to assess the integrity of the device is desirable. This study compares the device function by both objective and behavioural techniques in 30 children (age at implantation 3-11 years) at five years post-implantation. All children were implanted with the Nucleus Mini 22 device. Objective data were collected from integrity testing (IT) which allowed examination of the functioning of the implant by measuring the electrical stimulus artefact. This does not require the child to give a behavioural response. A protocol for a five-year post-implantation IT is suggested which examines common ground, monopolar and bipolar modes of operation. Behavioural data in the form of threshold (T) and comfort (C) levels were obtained by use of developmental age-appropriate techniques at 5 years post-implantation. Results demonstrate that 43.3% of patients had no electrode faults, 23.3% had potential faults on both behavioural and integrity testing, 6.7% were difficult to assess in terms of defining electrode faults due to partial electrode insertions, 13.3% had potential faults on behavioural testing only and 13.3% of patients had potential faults on IT only. In conclusion, IT is valuable in the identification of faulty electrodes, especially in young children and those with additional disabilities. Implementation of the five-year routine IT affected the management of 30% of patients. This study demonstrates that objective and behavioural techniques are complementary procedures in the ongoing management of paediatric patients.

This paper covers the design, development and operation of a novel piece of equipment, based around the CMA/12 guide probe (Carnegie Medicin, Sweden), which offers a low cost alternative for monitoring EEG at the site of microdialysis in a freely moving animal. This equipment is entirely based on commercially available parts, and thus can be easily replicated. Moreover, it is less intrusive than earlier models, offering advantages for experiments in which behavioural testing or chronic monitoring is required. We illustrate its use in a study of changes in electrical seizure activity, in both cortex and basal nuclei, evoked by the administration of the chemoconvulsant soman. The inference from the many experimental paradigms looking at the mechanisms of chemoconvulsants is that paroxysmal discharges are a better correlate of seizure activity than behavioural signs. The correlation of the EEG with extracellular neurotransmitter data, over a period of hours post-injection of chemoconvulsant, allows the determination of whether extracellular neurotransmitter changes are a cause or consequence of the evoked electrical activity.

In 1968, Melzack and Casey published a pivotal paper in which they described a model of the sensory, motivational and cognitive determinants of pain. Much of Ronald Melzack's career has been dedicated to exploring this complex relationship. Of primary importance is the influence that Ron has had on the development of some of the current research interests of the present author. For instance, Ron's theoretical approach provided the underpinnings for the development of an additional behavioural testing technique in rat models of nociception that has been recently developed in the author's laboratory. The test is based on the assumption that escape and avoidance of a stimulus are clear indications that the stimulus is aversive. It is proposed that behavioural test paradigms based on this approach provide additional information beyond the traditional measures of stimulus-evoked reflexive responses. With these tests, the underlying assumption that different aspects of pain are processed by different neural substrates can be tested.

The paper deals with the most important items regarding the improvement of quality of experimental procedures when testing drug effects on behaviour and development of commonly-used rodent species. Current-used test procedures for immature and adult rodents exposed early developmentally are briefly described and recent advances and difficulties in their hands-on interpretation are highlighted. Comparability of measures in human and animals for drug-effect assessment is also shortly discussed. It is then stressed that studies on rodents carried out in seminaturalistic and naturalistic settings may offer a highly profitable direction for future research in behavioural teratology and toxicology. A final paragraph is dedicated to the bioethical aspects arisen from the use of large number of rodents subjects in behavioural testing.

The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the euphoric effects of nicotine. The aim of the present experiment was to examine effects of chronic exposure to caffeine on responding maintained by nicotine. Sprague-Dawley rats consuming caffeine (approximately 150-180 mg/kg per day) in their drinking water for 7 days prior to the beginning and throughout behavioural testing acquired intravenous nicotine self-administration (0.03 mg/kg per infusion) more rapidly than did controls. In a cross-over design, exclusion of caffeine brought levels of nicotine self-administration back to baseline, while adding caffeine to the drinking water of control rats increased responding maintained by nicotine over 90%. These findings strongly suggest that caffeine can potentiate the reinforcing properties of nicotine, thus highlighting the importance of environmental factors in shaping and maintaining tobacco smoking.

Intense magnetic fields have been shown to affect memory-related behaviours of rodents. A series of experiments was performed to investigate further the effects of a 50 Hz magnetic field on the foraging behaviour of adult, male C57BL/6J mice performing a spatial learning task in an eight-arm radial maze. Exposure to vertical, sinusoidal magnetic fields between 7.5 mT and 7.5 mT for 45 min immediately before daily testing sessions caused transient decreases in performance that depended on the applied flux density. Exposure above a threshold of between 7.5 and 75 mT significantly increased the number of errors the animals made and reduced the rate of acquisition of the task without any effect on overall accuracy. However, the imposition of a 45-minute delay between exposure at 0.75 mT and behavioural testing resulted in the elimination of any deficit. Similarly, exposure to fields between 7.5mT and 0.75 mT for 45 min each day for 4 days after training had no amnesic effects on the retention and subsequent performance of the task. Overall, these results provide additional evidence that 50 Hz magnetic fields may cause subtle changes in the processing of spatial information in mice. Although these effects appear dependent on field strength, even at high flux densities the field-induced deficits tend to be transient and reversible. Bioelectromagnetics 19:486 ‐ 493, 1998. q 1998 Wiley-Liss, Inc.

Aggressive behaviour in dogs is an increasing problem in The Netherlands. In an attempt to find a solution to this problem the Dutch Ministry of Agriculture, Conservation and Fisheries has financially supported a study aimed at developing an aggression test for dogs. The primary goal is to use the test as an instrument for excluding very aggressive individuals of certain breeds from breeding. On the basis of two pilot studies a test has been developed with 43 sub-tests in which a variety of stimuli are presented relating to contexts that are known to elicit aggression in dogs. In the final test, 112 dogs, 75 of which were potentially aggressive breeds (PAB) and a group of 37 "control dogs", were tested. Questionnaires were used to collect information about the aggressive history of the dog. The results show clear differences in the aggression-eliciting properties of the sub-tests. Dogs with and without biting history differ significantly in their biting/attack behaviour during the test (Mann-Whitney U-test, P = 0.02). This difference is also found for only the PAB-dogs (MWU-test, P = 0.007). For reliability of analysis, 37 dogs were re-tested. The comparison between test and re-test shows a significant correlation for total attack (SPCC = 0.78) and biting/attack (SPCC = 0.68). So that the test can be implemented in practice, two "Models for Unacceptable Aggression (MUAs)" are discussed. To validate the results of the test and the application of the MUAs the results are compared with the biting history of the dogs. The results of an MUA based exclusively on the biting/attack behaviour shows a significant relation with the biting history for all dogs and for the PAB-dogs. On the basis of these results we consider the test to be a useful instrument for the assessment of aggressive tendencies in dogs, provided the test is performed by trained researchers or trained judges and test assistants.

This dissertation describes separate but related studies that explore visual spatial learning and memory in Fragile X Syndrome. Across all studies, either the performance of individuals affected by FXS and/or fmr1 KO mice was compared to comparison controls on seven H-W mazes of increasing difficulty levels. Study one employed the traditional configuration of the H-W mazes to evaluate performance variables that include latency to complete the maze and number of the errors. The results of study 1 revealed significant differences in performance for both FXS groups as compared to mental age-matched comparison individuals and wild type mice, respectively. In contrast to the FXS group, performance of the comparison group improved as indicated by significantly fewer errors across trials. A similar pattern of results was observed when latency across trials was analyzed. Taken together, the results of study one support the hypothesis that a selective deficit in spatial learning and memory characteristic of the FXS phenotype can be observed in the murine model of FXS, if equivalent tasks are employed in testing humans and mice. Study two expanded on these findings by adding landmarks to the maze environment to evaluate how these may impact spatial learning and memory in fmr1 KO mice. Contrary to our hypotheses, landmarks significantly impaired wild type control performance. In addition, results revealed that the performance of the fmr1 KO mice generally did not differ between landmark and non-landmark tasks, indicating that the presence of landmarks neither enhanced nor hindered mouse performance. Lastly, study three entailed a more in-depth behavior analysis of maze navigation performance for FXS individuals from study 1. Consistent with the hypotheses and findings from study 1, results revealed significant differences in performance variables between individuals, with FXS participants generally performing worse than the comparison group participants. Taken together, the results of study 3 generally supported the hypothesis that there was greater impairment in performance for individuals affected by FXS as compared to controls. This impairment was evident in the pattern of pathways taken to solve H-W mazes, consistent with the notion that affected individuals employed different behavioral strategies.

This study set out to determine the accuracy with which tone pip ABR and click ABR, carried out in babies referred from universal newborn hearing screening, is able to predict the hearing outcome as determined by follow-up hearing tests.The cohort of babies studied were all babies referred for hearing assessment from the universal newborn hearing screen in Sheffield, UK for the period January 2002 to September 2007, who were found to have a significant hearing impairment.The results of hearing assessment following referral from the newborn hearing screen were collected together with those of follow-up tests carried out up to an age when behavioural testing had established ear- and frequency-specific thresholds at 0.5, 1, 2 and 4 kHz.The standard deviation of the difference between the follow up and the tone pip ABR thresholds was 10.5 dB for the 4-kHz tone pip, 16.8 dB for the 1-kHz tone pip, and ranged between 21.7 and 24.7 dB for click ABR.The results of the study show that tone pip ABR following referral from newborn hearing screening has a similar accuracy to that reported in older subjects, and is a much better predictor compared to click ABR.

Background: Disruption of circadian rhythms is associated with several deleterious health consequences and cognitive impairment. It is estimated that as many as one in five workers are exposed to this risk factor due to experiencing some degree of chronodisruption by way of recurring patterns of shift work. It is not presently clear therefore how efficiently the mammalian circadian system entrains to alternative light/dark cycles such as those found in shift work schedules. Methods: The present study examines male CD-1 mice exposed to three different paradigms of rapidly rotating shift work-like light/dark manipulations compared to control animals maintained on a standard 12:12 h light/dark cycle. Results: Analysis of circadian patterns of behaviour under such conditions reveals that for fast rotating schedules of light/dark there is minimal circadian entrainment. Further, when placed in constant conditions after a period under the “shift work” lighting conditions there were changes to circadian period associated with the shift work schedules. In contrast to previous studies the shift work-like conditions did not produce changes in animal bodyweight. Behavioural testing suggests possible anxiogenic and hyperactive outcomes dependent on rotation speed as animals displayed open field thigmotaxis and hyperlocomotion. Conclusion: These results indicate that exposure to alternating patterns of light and dark as experienced by millions of shift workers may produce long-lasting changes in both mammalian circadian and neurobehavioural systems.

BackgroundTo date, experimental and preclinical studies on neuropsychiatric conditions have almost exclusively been performed in experimentally-induced animal models and have only rarely relied upon an ethological approach where animals have been observed in more naturalistic settings. The laboratory species of choice has been the rodent while the potential of more closely-related non-human primates have remained largely underexplored.MethodsThe present study, therefore, aimed at investigating the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 cynomolgus macaques in captive conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence analysis and a hierarchical clustering.ResultsThe study identified five distinct profiles (groups A to E) that significantly differed on several behaviours, body postures, body orientations, gaze directions and locations in the cage environment. We suggest that animals from the low n groups (D and E) present depressive-like and anxious-like symptoms, reminiscent of depressive and generalized anxiety disorders. Inter-individual differences were highlighted through unbiased ethological observations of spontaneous behaviours and associated parameters, although these were not associated with differences in plasma or cerebrospinal fluid levels of either stress-related hormones or monoamines, i.e. in accordance with the human situation.ConclusionsNo interventional behavioural testing was required to discriminate between 3 typical and 2 atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like and anxiety-like symptoms. The use of unbiased behavioural observations might, thus, allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.