Oculomotor Abnormalities in a Sheep (Ovis aries) Model of Huntington's Disease: Towards a Biomarker for Assessing Therapeutic Efficacy.

Background: Huntington's disease (HD) is characterized by a loss of control of motor function that causes the presence of abnormal eye movements at early stages.

Objective: To determine if, compared to normal sheep, HD sheep have abnormal eye movements.

Methods: We measured eye movements in a transgenic sheep (Ovis aries) model of HD using a purpose-built, head-mounted sheep oculometer.

Risk factors for stereotypic behaviour in captive ungulates.

Behavioural needs are highly motivated actions critical to a species survival and reproduction. Prolonged restriction of these behaviours can lead to stereotypic behaviours (SB) in captive animals, and this is particularly common in ungulate species. While risk factors for SB have been suggested for some ungulates, no study has integrated these findings to identify which aspects of ungulates' wild behavioural biology and captive husbandry are potential drivers for SB across this clade.

The effects of two stressors on working memory and cognitive flexibility in zebrafish (Danio rerio): The protective role of D1/D5 agonist on stress responses.

Acute stressors are recurrent in multiple species' lives and can facilitate or impair cognition. The use of zebrafish (Danio rerio) as a translational species to understand the mechanisms by which stress induces different behavioral phenotypes has been widely studied. Two acute stressors are recognized when using this species: (1) conspecific alarm substance (CAS); and (2) net chasing.

Blink rate as a measure of stress and attention in the domestic horse (Equus caballus).

Measuring animal stress is fundamentally important for assessing animal emotional state and welfare. Conventional methods of quantifying stress (cortisol levels, heart rate/heart rate variability) require specialist equipment and are not instantly available. Spontaneous blink rate (SBR) has previously been used to measure stress responses in humans and may provide a non-invasive method for measuring stress in other animal species.

The Free-movement pattern Y-maze: A cross-species measure of working memory and executive function.

Numerous neurodegenerative and psychiatric disorders are associated with deficits in executive functions such as working memory and cognitive flexibility. Progress in developing effective treatments for disorders may benefit from targeting these cognitive impairments, the success of which is predicated on the development of animal models with validated behavioural assays. Zebrafish offer a promising model for studying complex brain disorders, but tasks assessing executive function are lacking.

Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders.

Abnormal repetitive behaviors (ARBs) are a prominent symptom of numerous human brain disorders and are commonly seen in rodent models as well. While rodent studies of ARBs continue to dominate the field, mounting evidence suggests that zebrafish (Danio rerio) also display ARB-like phenotypes and may therefore be a novel model organism for ARB research. In addition to clear practical research advantages as a model species, zebrafish share high genetic and physiological homology to humans and rodents, including multiple ARB-related genes and robust behaviors relevant to ARB.

Indices of comparative cognition: assessing animal models of human brain function.

Understanding the cognitive capacities of animals is important, because (a) several animal models of human neurodegenerative disease are considered poor representatives of the human equivalent and (b) cognitive capacities may provide insight into alternative animal models. We used a three-stage process of cognitive and neuroanatomical comparison (using sheep as an example) to assess the appropriateness of a species to model human brain function. First, a cognitive task was defined via a reinforcement-learning algorithm where values/constants in the algorithm were taken as indirect measures of neurophysiological attributes.

Causal and functional interpretation of mu- and delta-opioid receptor profiles in mesoaccumbens and nigrostriatal pathways of an oral stereotypy phenotype.

Spontaneous stereotypic behaviours are repetitive, compulsive, topographically invariant response patterns commonly observed in captive or domestic animals, which have been linked to dysfunction of basal ganglia input/output pathways. There is evidence that endogenous opioids play a key regulatory role in basal ganglia direct and indirect pathways, but their precise role, both causally and functionally, in spontaneous stereotypic behaviour is unclear. Here we examined the profile of mu- and delta-opioid receptors (density [Bmax] and affinity [Kd]) of basal ganglia structures in stereotypy (n = 10) and non-stereotypy (n = 10) animals using a competitive ligand binding approach.

A stop-signal task for sheep: introduction and validation of a direct measure for the stop-signal reaction time.

Huntington's disease (HD) patients show reduced flexibility in inhibiting an already-started response. This can be quantified by the stop-signal task. The aim of this study was to develop and validate a sheep version of the stop-signal task that would be suitable for monitoring the progression of cognitive decline in a transgenic sheep model of HD.

Developing a 3-choice serial reaction time task for examining neural and cognitive function in an equine model.

Background: Large animal models of human neurological disorders are advantageous compared to rodent models due to their neuroanatomical complexity, longevity and their ability to be maintained in naturalised environments. Some large animal models spontaneously develop behaviours that closely resemble the symptoms of neural and psychiatric disorders. The horse is an example of this; the domestic form of this species consistently develops spontaneous stereotypic behaviours akin to the compulsive and impulsive behaviours observed in human neurological disorders such as Tourette's syndrome.

Neural modulators of temperament: A multivariate approach to personality trait identification in the horse.

A relationship between dopamine and temperament has previously been described in human cases of dopaminergic dysfunction. Adjustment in temperament prior to disease manifestation can enable the early identification of individuals at risk of such conditions, and scope exists to extend this application of temperament alterations to cases of dopaminergic dysfunction in horses. A multivariate and mixed-methods approach utilising a questionnaire along with two inferred measurements of dopamine activity (Spontaneous Blink Rate [SBR] and behavioral initiation rate [BIR]) were recorded from direct observation of animals (n=99) to identify the potential relationship between dopamine and temperament in horses.

A mobile, high-throughput semi-automated system for testing cognition in large non-primate animal models of Huntington disease.

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 disrupted basal ganglia and behavioural control: an integrative cross-domain perspective of spontaneous stereotypy.

Spontaneous stereotypic behaviour (SB) is common in many captive animal species, as well as in humans with some severe psychiatric disorders, and is often cited as being related to general basal ganglia dysfunction. Despite this assertion, there is little in the literature examining SB specifically in terms of the basal ganglia mechanics. In this review, we attempt to fill this gap by offering an integrative, cross-domain perspective of SB by linking what we currently understand about the SB phenotype with the ever-growing literature on the anatomy and functionality of the basal ganglia.

Psychological factors affecting equine performance.

For optimal individual performance within any equestrian discipline horses must be in peak physical condition and have the correct psychological state. This review discusses the psychological factors that affect the performance of the horse and, in turn, identifies areas within the competition horse industry where current behavioral research and established behavioral modification techniques could be applied to further enhance the performance of animals. In particular, the role of affective processes underpinning temperament, mood and emotional reaction in determining discipline-specific performance is discussed.

Differential place and response learning in horses displaying an oral stereotypy.

Significant similarities exist between the neural and behavioural features of environmentally and drug-induced stereotypy. For example, exposure to dopamine agonists, such as amphetamine, induces stereotypy and causes alterations in midbrain neurophysiology similar to those observed following chronic stress. An additional behavioural feature of these neural changes in the drug-induced phenotype is an enhanced rate of switching from response-outcome (R-O) to stimulus-response (S-R) learning.

Impaired instrumental choice in crib-biting horses (Equus caballus).

Horses displaying an oral stereotypy were tested on an instrumental choice paradigm to examine differences in learning from non-stereotypic counterparts. Stereotypic horses are known to have dysfunction of the dorsomedial striatum, and lesion studies have shown that this region may mediate response-outcome learning. The paradigm was specifically applied in order to examine learning that requires maintenance of response-outcome judgements.