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.

Low-dose memantine-induced working memory improvement in the allothetic place avoidance alternation task (APAAT) in young adult male rats.

N-methyl-D-aspartate receptors (NMDAR) are involved in neuronal plasticity. To assess their role simultaneously in spatial working memory and non-cognitive learning, we used NMDAR antagonists and the Allothetic Place Avoidance Alternation Task (APAAT). In this test rats should avoid entering a place where shocks were presented on a rotating arena which requires cognitive coordination for the segregation of stimuli. The experiment took place 30 min after intraperitoneal injection of memantine (5, 10, 20 mg/kg b.w.: MemL, MemM, MemH, respectively) and (+)MK-801 (0.1, 0.2, 0.3 mg/kg b.w.: MK-801L, MK-801M, MK-801H, respectively). Rats from the control group were intact or injected with saline (0.2 ml/kg). Over three consecutive days the rats underwent habituation, two avoidance training intervals with shocks, and a retrieval test. The shock sector was alternated daily. The after-effects of the agents were tested on Day 21. Rats treated with low dose memantine presented a longer maximum time avoided and fewer entrances than the MemH, MK-801M, MK-801H and Control rats. The shocks per entrances ratio, used as an index of cognitive skill learning, showed skill improvement after D1, except for rats treated by high doses of the agents. The activity levels, indicated by the distance walked, were higher for the groups treated with high doses of the agents. On D21 the MK801H rats performed the memory task better than the MemH rats, whereas the rats' activity depended on condition, not on the group factor. These results suggest that in naïve rats mild NMDAR blockade by low-dose memantine improves working memory related to a highly challenging task.

Cumulative benefits of frontal transcranial direct current stimulation on visuospatial working memory training and skill learning in rats.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex, which non-invasively alters cortical activity, has been established to affect executive functions in humans. We hypothesized that changes in excitability by tDCS, found to improve cognitive functions dependent on moderate prefrontal cortex activity, would operate similarly in animals as in humans. To verify this we performed experiments using a rat behavioral model of visuospatial working memory and skill learning paired with tDCS of the frontal cortex. The effect of anodal/cathodal tDCS was examined in three sessions using the allothetic place avoidance alternation task (APAAT) and later re-examined without stimulation. Stimulation had no measurable short term effect on on-going place avoidance learning. However, in the follow-up session on day 21 the rats previously treated with cathodal tDCS showed significantly more efficient place avoidance and skill retention in comparison to the controls. This demonstrates a long-term benefit of diminished excitability by frontal tDCS when paired with training on working memory and skill learning in a novel task. The presented behavioral model provides a tool to evaluate the underlying mechanisms of how tDCS modulates neural network function to support successful behavior.

A spatial paradigm, the allothetic place avoidance alternation task, for testing visuospatial working memory and skill learning in rats.

We present a paradigm for assessing visuospatial working memory and skill learning in a rodent model, based on the place avoidance test. In our allothetic place avoidance alternation task (APAAT) the paradigm is comprised of minimal training sessions, tests various aspects of learning and memory and provides a rich set of parameters. A single working memory session consists of four conditions: habituation (no shock), two place avoidance training intervals (shock activated) and a retrieval test (shock inactivated). The location of the shock sector is alternated for each training day which initially requires extinction of previous representations and further working memory to achieve effective place avoidance across sessions. Visuospatial skill memory was evaluated by the shock/entrance ratio by tracking locomotor activity which is essential to execute a place avoidance strategy. For each day rats learned to avoid a new place with shock, as shown by a decreased number of entrances, and an increased time to the first entrance and maximum avoidance time. Skill learning improved according to the decreased number of shocks per entrance across conditions. These results indicate that complex cognitive functions are captured by this behavioral method. This APAAT paradigm expands and complements existing tools for studying hippocampal-prefrontal dependent functions to support development of treatment interventions.