Learning to recognize rat social behavior: Novel dataset and cross-dataset application.

BACKGROUND: Social behavior is an important aspect of rodent models. Automated measuring tools that make use of video analysis and machine learning are an increasingly attractive alternative to manual annotation. Because machine learning-based methods need to be trained, it is important that they are validated using data from different experiment settings. NEW METHOD: To develop and validate automated measuring tools, there is a need for annotated rodent interaction datasets. Currently, the availability of such datasets is limited to two mouse datasets. We introduce the first, publicly available rat social interaction dataset, RatSI. RESULTS: We demonstrate the practical value of the novel dataset by using it as the training set for a rat interaction recognition method. We show that behavior variations induced by the experiment setting can lead to reduced performance, which illustrates the importance of cross-dataset validation. Consequently, we add a simple adaptation step to our method and improve the recognition performance. COMPARISON WITH EXISTING METHODS: Most existing methods are trained and evaluated in one experimental setting, which limits the predictive power of the evaluation to that particular setting. We demonstrate that cross-dataset experiments provide more insight in the performance of classifiers. CONCLUSIONS: With our novel, public dataset we encourage the development and validation of automated recognition methods. We are convinced that cross-dataset validation enhances our understanding of rodent interactions and facilitates the development of more sophisticated recognition methods. Combining them with adaptation techniques may enable us to apply automated recognition methods to a variety of animals and experiment settings.

Home-cage anxiety levels in a transgenic rat model for Spinocerebellar ataxia type 17 measured by an approach-avoidance task: The light spot test.

BACKGROUND: Measuring anxiety in a reliable manner is essential for behavioural phenotyping of rodent models such as the rat model for Spinocerebellar ataxia type 17 (SCA17) where anxiety is reported in patients. An automated tool for assessing anxiety within the home cage can minimize human intervention, stress of handling, transportation and novelty. NEW METHOD: We applied the anxiety test "light spot" (LS) (white led directed at the food-hopper) to our transgenic SCA17 rat model in the PhenoTyper 4500® to extend the knowledge of this automated tool for behavioural phenotyping and to verify an anxiety-like phenotype at three different disease stages for use in future therapeutic studies. RESULTS: Locomotor activity was increased in SCA17 rats at 6 and 9 months during the first 15min of the LS, potentially reflecting increased risk assessment. Both genotypes responded to the test with lower duration in the LS zone and higher time spent inside the shelter compared to baseline. COMPARISON WITH EXISTING METHODS: We present the first data of a rat model subjected to the LS. The LS can be considered more biologically relevant than a traditional test as it measures anxiety in a familiar situation. CONCLUSIONS: The LS successfully evoked avoidance and shelter-seeking in rats. SCA17 rats showed a stronger approach-avoidance conflict reflected by increased activity in the area outside the LS. This home cage test, continuously monitoring pre- and post-effects, provides the opportunity for in-depth analysis, making it a potentially useful tool for detecting subtle or complex anxiety-related traits in rodents.

The BACHD Rat Model of Huntington Disease Shows Specific Deficits in a Test Battery of Motor Function.

Rationale: Huntington disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype. Objective: The present study aims to characterize different aspects of motor function in BACHD rats, combining classical paradigms with novel high-throughput behavioral phenotyping. Methods: Wild-type (WT) and transgenic animals were tested longitudinally from 2 to 12 months of age. To measure fine motor control, rats were challenged with the pasta handling test and the pellet reaching test. To evaluate gross motor function, animals were assessed by using the holding bar and the grip strength tests. Spontaneous locomotor activity and circadian rhythmicity were assessed in an automated home-cage environment, namely the PhenoTyper. We then integrated existing classical methodologies to test motor function with automated home-cage assessment of motor performance. Results: BACHD rats showed strong impairment in muscle endurance at 2 months of age. Altered circadian rhythmicity and locomotor activity were observed in transgenic animals. On the other hand, reaching behavior, forepaw dexterity and muscle strength were unaffected. Conclusions: The BACHD rat model exhibits certain features of HD patients, like muscle weakness and changes in circadian behavior. We have observed modest but clear-cut deficits in distinct motor phenotypes, thus confirming the validity of this transgenic rat model for treatment and drug discovery purposes.

Anxiety and risk assessment-related traits in a rat model of Spinocerebellar ataxia type 17.

Anxiety as a common feature of several neurodegenerative/polyglutamine diseases is an important aspect for the face validity of an animal model for Spinocerebellar Ataxia type 17 (SCA17). Risk assessment and anxiety-like traits were characterised in 3-6-9 months old rats of a transgenic model for SCA17 using the standard behavioural test elevated plus maze. In addition, c-Fos immunostainings in the basolateral amygdala evaluated neuronal activation in correlation to the behavioural responses. The most prominent behavioural effect was a higher level of risk assessment in the transgenic rats. In addition, an increase in anxiety-related behaviour in these rats was found. Although the EPM caused no overall effect on c-Fos expression, a negative correlation with the anxiety-like behavioural response was observed. Our results suggest that the SCA17 rat model displays an anxious phenotype already at 3 months of age resembling the generalized anxiety in early symptomatic SCA17 patients, thus confirming the validity of this rat model.

Automated quantitative analysis to assess motor function in different rat models of impaired coordination and ataxia.

BACKGROUND: An objective and automated method for assessing alterations in gait and motor coordination in different animal models is important for proper gait analysis. The CatWalk system has been used in pain research, ischemia, arthritis, spinal cord injury and some animal models for neurodegenerative diseases. NEW METHOD: Our goals were to obtain a comprehensive gait analysis of three different rat models and to identify which motor coordination parameters are affected and are the most suitable and sensitive to describe and detect ataxia with a secondary focus on possible training effects. RESULTS: Both static and dynamic parameters showed significant differences in all three models: enriched housed rats show higher walking and swing speed and longer stride length, ethanol-induced ataxia affects mainly the hind part of the body, and the SCA17 rats show coordination disturbances. Coordination changes were revealed only in the case of the ethanol-induced ataxia and the SCA17 rat model. Although training affected some gait parameters, it did not obscure group differences when those were present. COMPARISON WITH EXISTING METHODS: To our knowledge, a comparative gait assessment in rats with enriched housing conditions, ethanol-induced ataxia and SCA17 has not been presented before. CONCLUSIONS: There is no gold standard for the use of CatWalk. Dependent on the specific effects expected, the protocol can be adjusted. By including all sessions in the analysis, any training effect should be detectable and the development of the performance over the sessions can provide insight in effects attributed to intervention, treatment or injury.