Constitutive differences in glucocorticoid responsiveness are related to divergent spatial information processing abilities.

The stress response facilitates survival through adaptation and is intimately related to cognitive processes. The Morris water maze task probes spatial learning and memory in rodents and glucocorticoids (i.e. corticosterone (CORT) in rats) have been suggested to elicit a facilitating action on memory formation. Moreover, the early aging period (around 16-18 months of age) is susceptible to stress- and glucocorticoid-mediated acceleration of cognitive decline. In this study, we tested three lines of rats selectively bred according to their individual differences in CORT responsiveness to repeated stress exposure during juvenility. We investigated whether endogenous differences in glucocorticoid responses influenced spatial learning, long-term memory, and reversal learning abilities in a Morris water maze task at early aging. Additionally, we assessed the quality of the different swimming strategies of the rats. Our results indicate that rats with differential CORT responsiveness exhibit similar spatial learning abilities but different long-term memory retention and reversal learning. Specifically, the high CORT responding line had a better long-term spatial memory, while the low CORT responding line was impaired for both long-term retention and reversal learning. Our modeling analysis of performance strategies revealed further important line-related differences. Therefore, our findings support the view that individuals with high CORT responsiveness would form stronger long-term memories to navigate in stressful environments. Conversely, individuals with low CORT responsiveness would be impaired at different phases of spatial learning and memory.

Strategies discovery in the active allothetic place avoidance task.

The Active Allothetic Place Avoidance task is an alternative setup to Morris Water Maze that allows studying spatial memory in a dynamic world in the presence of conflicting information. In this task, a rat, freely moving on a rotating circular arena, has to avoid a sector defined within the room frame where shocks are presented. While for Morris Water Maze several studies have identified animal strategies which specifically affect performance, there were no such studies for the Active Allothetic Place Avoidance task. Using standard machine learning methods, we were able to reveal for the first time, to the best of our knowledge, explainable strategies that the animals employ in this task and demonstrate that they can provide a high-level interpretation for performance differences between an animal group treated with silver nanoparticles (AgNPs) and the control group.

Behavioral characteristics as potential biomarkers of the development and phenotype of epilepsy in a rat model of temporal lobe epilepsy.

The present study performed a detailed analysis of behavior in a rat model of epilepsy using both established and novel methodologies to identify behavioral impairments that may differentiate between animals with a short versus long latency to spontaneous seizures and animals with a low versus high number of seizures. Temporal lobe epilepsy was induced by electrical stimulation of the amygdala. Rats were stimulated for 25 min with 100-ms trains of 1-ms biphasic square-wave pluses that were delivered every 0.5 s. Electroencephalographic recordings were performed to classify rats into groups with a short latency (< 20 days, n = 7) and long latency (> 20 days, n = 8) to the first spontaneous seizure and into groups with a low number of seizures (62 ± 64.5, n = 8) and high number of seizures (456 ± 185, n = 7). To examine behavioral impairments, we applied the following behavioral tests during early and late stages of epilepsy: behavioral hyperexcitability, open field, novel object exploration, elevated plus maze, and Morris water maze. No differences in stress levels (e.g., touch response in the behavioral hyperexcitability test), activity (e.g., number of entries into the open arms of the elevated plus maze), or learning (e.g., latency to find the platform in the Morris water maze test during training days) were observed between animals with a short versus long latency to develop spontaneous seizures or between animals with a low versus high number of seizures. However, we found a higher motor activity measured by higher number of entries into the closed arms of the elevated plus maze at week 26 post-stimulation in animals with a high number of seizures compared with animals with a low number of seizures. The analysis of the Morris water maze data categorized the strategies that the animals used to locate the platform showing that the intensity of epilepsy and duration of epileptogenesis influenced swimming strategies. These findings indicate that behavioral impairments were relatively mild in the present model, but some learning strategies may be useful biomarkers in preclinical studies.

Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish.

Diabetes is associated with dysfunction of the neurovascular unit, although the mechanisms of this are incompletely understood and currently no treatment exists to prevent these negative effects. We previously found that the nitric oxide (NO) donor sodium nitroprusside (SNP) prevents the detrimental effect of glucose on neurovascular coupling in zebrafish. We therefore sought to establish the wider effects of glucose exposure on both the neurovascular unit and on behaviour in zebrafish, and the ability of SNP to prevent these. We incubated 4-days post-fertilisation (dpf) zebrafish embryos in 20 mM glucose or mannitol for 5 days until 9 dpf, with or without 0.1 mM SNP co-treatment for 24 h (8-9 dpf), and quantified vascular NO reactivity, vascular mural cell number, expression of a klf2a reporter, glial fibrillary acidic protein (GFAP) and transient receptor potential cation channel subfamily V member 4 (TRPV4), as well as spontaneous neuronal activation at 9 dpf, all in the optic tectum. We also assessed the effect on light/dark preference and locomotory characteristics during free-swimming studies. We find that glucose exposure significantly reduced NO reactivity, klf2a reporter expression, vascular mural cell number and TRPV4 expression, while significantly increasing spontaneous neuronal activation and GFAP expression (all in the optic tectum). Furthermore, when we examined larval behaviour, we found that glucose exposure significantly altered light/dark preference and high and low speed locomotion while in light. Co-treatment with SNP reversed all these molecular and behavioural effects of glucose exposure. Our findings comprehensively describe the negative effects of glucose exposure on the vascular anatomy, molecular phenotype and function of the optic tectum, and on whole-organism behaviour. We also show that SNP or other NO donors may represent a therapeutic strategy to ameliorate the complications of diabetes on the neurovascular unit.This article has an associated First Person interview with the first author of the paper.

A generalised framework for detailed classification of swimming paths inside the Morris Water Maze.

The Morris Water Maze is commonly used in behavioural neuroscience for the study of spatial learning with rodents. Over the years, various methods of analysing rodent data collected during this task have been proposed. These methods span from classical performance measurements to more sophisticated categorisation techniques which classify the animal swimming path into behavioural classes known as exploration strategies. Classification techniques provide additional insight into the different types of animal behaviours but still only a limited number of studies utilise them. This is primarily because they depend highly on machine learning knowledge. We have previously demonstrated that the animals implement various strategies and that classifying entire trajectories can lead to the loss of important information. In this work, we have developed a generalised and robust classification methodology to boost classification performance and nullify the need for manual tuning. We have also made available an open-source software based on this methodology.