New information is rarely learned in isolation, instead most of what we experience can be incorporated into previous knowledge networks. However, most rodent laboratory tasks assume the animal to be naïve with no previous experience influencing the results, which may be a factor contributing to the current crisis of translational failure when going from the basic lab to human research. Previous research in rats has indicated, that previous knowledge in form of a schema can facilitate knowledge acquisition and accelerate systems consolidation: memories become more rapidly hippocampal independent and instead rely on the prefrontal cortex. These results emphasized the need for more tasks that investigate previous knowledge effects and can be applied in both rats and mice. Here, we developed a new spatial navigation task, training food locations in a large, gang-way maze – the Hex Maze. We can show simple memory effects as well as multiple effects of previous knowledge accelerating both online learning as well as performance increases during offline periods. These effects are reminiscent of both Learning-Set and Schema, two different previous knowledge effects described previously in the literature.
In sum, with the Hex-Maze we have developed a flexible rodent task in which different effects of previous knowledge on memory performance, encoding and updating can be investigated.
Declarative memory encompasses representations of specific events as well as knowledge extracted by accumulation over multiple episodes. To investigate how these different sorts of memories are created, we developed a new behavioral task in rodents. The task consists of 3 distinct conditions (stable, overlapping, and random). Rodents are exposed to multiple sample trials, in which they explore objects in specific spatial arrangements, with object identity changing from trial to trial. In the stable condition, the locations are constant during all sample trials even though the objects themselves change; in the test trial, 1 object’s location is changed. In the random condition, object locations are presented in the sample phase without a specific spatial pattern. In the overlapping condition, 1 location is shared (overlapping) between all trials, while the other location changes during sample trials. We show that in the overlapping condition, instead of only remembering the last sample trial, rodents form a cumulative memory of the sample trials. We could show that both mice and rats can accumulate information across multiple trials and express a long-term abstracted memory (Genzel et al Plos Bio 2019).
The well being of laboratory animals is an issue of crucial importance. In our lab we avoid tail pick-ups for mice (we only use cupping or tubing to move) in order to relieve animal from stress and pain. All animals are thoroughly handled and habituated to experimenters before the start of any new project (see videos). Happier animals for a better science.
Electrophysiology is a key technique in our lab. We use it to get a picture of the instantaneous network activity by monitoring the activity of large set of neurons as well as local field potentials. We use tetrodes and silicon probes in rats and mice both in acute and chronic preparations. Systems in use are mainly open-ephys but also spike-gadgets for wire-less recordings.
In our lab we use different molecular methods. For example we measure activity dependent immediate early genes (immunohistochemistry and quantative PCR) and engram tagging techniques (TRAP2). Further, we use viral vectors to e.g. increase plasticity in selected brain areas.
In humans, we use functional MR Imaging as well as sleep-EEG recordings to investigate how sleep impacts on changes of activity in memory-related brain networks from encoding to retrieval. We have previously shown that in patients with depression and schizophrenia decreased hippocampal-prefrontal cortex connectivity during learning predicts sleep related memory deficits (Genzel et al. 2015).
Here at the Donders Institute we continue our investigations in healthy controls, with behavioural paradigms matching our rodent approaches.
