J Neurosci. 2023 Jun 21:JN-RM-2101-22. doi: 10.1523/JNEUROSCI.2101-22.2023. Online ahead of print.

ABSTRACT

The trial-unique non-matching to location (TUNL) touchscreen task shows promise as a translational assay of working memory deficits in rodent models of autism, ADHD, and schizophrenia. However, the low-level neurocognitive processes that drive behaviour in the TUNL task have not been fully elucidated. In particular, it is commonly assumed that the TUNL task predominantly measures spatial working memory dependent on hippocampal pattern separation, but this proposition has not previously been tested. In this project, we tested this question using computational modelling of behaviour from male and female mice performing the TUNL task (N=163 across three datasets; 158,843 trials). Using this approach, we empirically tested whether TUNL behaviour solely measured retrospective working memory, or whether it was possible to deconstruct behaviour into additional neurocognitive subprocesses. Overall, contrary to common assumptions, modelling analyses revealed that behaviour on the TUNL task did not primarily reflect retrospective spatial working memory. Instead, behaviour was best explained as a mixture of response strategies including both retrospective working memory (remembering the spatial location of a previous stimulus) and prospective working memory (remembering an anticipated future behavioral response) as well as animal-specific response biases. These results suggest that retrospective spatial working memory is just one of a number of cognitive subprocesses that contribute to choice behaviour on the TUNL task. We suggest that findings can be understood within a resource-rational framework, and use computational model simulations to propose several task-design principles that we predict will maximise spatial working memory and minimise alternative behavioural strategies in the TUNL task.Significance statementTouchscreen tasks represent a paradigm shift for assessment of cognition in non-human animals by automating large-scale behavioral data collection. Their main relevance, however, depends on the assumption of functional equivalence to cognitive domains in humans. The trial-unique, delayed non-matching to location (TUNL) touchscreen task, has revolutionized the study of rodent spatial working memory. However, its assumption of functional equivalence to human spatial working memory is untested. We leveraged previously untapped single-trial TUNL data to uncover a novel set of hierarchically ordered cognitive processes that underlie mouse behavior on this task. The strategies employed demonstrate multiple cognitive approaches to a single behavioural outcome and the requirement for more precise task design and sophisticated data analysis in interpreting rodent spatial working memory.

PMID:37369587 | DOI:10.1523/JNEUROSCI.2101-22.2023