06 July 2020

Effects of D1 agonist on working memory and cognitive flexibility in a zebrafish model of aging

Matts Ymaze

A new preprint on bioRxiv used Zantiks AD units to measure search strategies in the FMP y-maze assay in order to investigate changes in working memory and cognitive flexibility between adulthood and old age in a zebrafish model. In a y-maze assay, an animal adopts certain 'search strategies' to explore the 3 arms of the 'Y'. Cleal et al. have previously identified that zebrafish use a specific strategy of exploration which primarily uses an alternation strategy and this strategy is subject to change over time (behavioural flexibility). Alternations are characterised predominantly by the animal alternating left and right turns throughout the run of the maze.

In this current paper, Cleal et al. found that 24 month old (aged) zebrafish, when compared to 6 month old (middle-aged) zebrafish, show a marked reduction in the use of alternations sequences (LRLR, RLRL). They suggest this reduction in alternations may represent an inability to remember which arms of the maze have previously been entered and/or the order of entry. This is a process previously shown to be dependent on working memory. Thus suggesting that zebrafish, like humans, have a natural decline in cognitive abilities as part of healthy aging, resulting in deficits in working memory.

Cleal et al. found that treatment with a partial D1/D5 (SKF-38393) agonist ameliorated this decline in working memory, shown through an increase in the use of alternations in 24 month old zebrafish, to a level comparable to 6 month old fish. The effect of SKF-38393 was age specific; no changes in working memory were observed in 6 month old zebrafish.

Researchers also found that 6 month old fish increased their use of alternations throughout the trial, but aged fish did not. This finding highlights an inability to adapt behaviour in response to the environment which is of importance in aging conditions. This effect of time on search strategy can be reduced following treatment with SKF-38393. In aging adults, who had lost the ability to adapt strategy over time, treatment with the D1-like receptor agonist was unable to restore this behaviour.

The Zantiks AD unit is a proven automated system for tracking and analysing adult zebrafish (and similarly sized fish) behaviour.

Effects of D1 agonist on working memory and cognitive flexibility in a zebrafish model of aging