Biology subjects

Cleal, M.

Publications and source records attributed to Cleal, M..

5 recordsLinked to original sources

bioRxiv2020

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

Healthy aging is associated with a decline in memory and executive function, which have both been linked with aberrant dopaminergic signalling. We examined the relationship between cognitive performance and dopamine function of young and aging zebrafish (Danio rerio). We revealed age-related decreases in working memory and cognitive flexibility in the Free-Movement Pattern (FMP) Y-maze. An increase in drd5 gene expression in aging adults coincided with a decrease in cognitive performance. Treatment with a D1/D5 receptor agonist (SKF-38393, 35 M) 30 minutes prior to behavioural assessment resulted in improved working memory in aging zebrafish, but no effect in younger adults. However, an overdosing effect caused by agonist treatment resulted in downregulation of dat expression in 6-month old, treated zebrafish. The translational relevance of these findings was tested in humans by analysing exploratory behaviour in young-adult, 18-35-year olds, and aged adults, 70+ year olds, in a virtual FMP Y-maze. Our findings revealed similar age-related decline in working memory. Thus, strongly supporting zebrafish as a translational model of aging and cognitive decline.

animal behavior and cognition↗

bioRxiv2020

Moderate early-life stress improves adult zebrafish (Danio rerio) spatial short-term memory but does not affect social and anxiety-like responses

Early-life stress (ELS) is defined as a short or chronic period of trauma, environmental or social deprivation, which can affect different neurochemical and behavioral patterns during adulthood. Zebrafish (Danio rerio) have been widely used as a model system to understand human neurodevelopmental disorders and display translationally relevant behavioral and stress-regulating systems. In this study, we aimed to investigate the effects of moderate ELS by exposing young animals (six weeks post-fertilization), for three consecutive days, to three stressors, and analyzing the impact of this on adult zebrafish behavior (sixteen weeks post-fertilization). The ELS impact in adults was assessed though analysis of performance on tests of unconditioned memory (free movement pattern Y-maze test), exploratory and anxiety-related task (novel tank diving test) and social cohesion (shoaling test). Here, we show for the first time that moderate ELS increases the number of pure alternations compared to pure repetitions in the unconditioned Y-maze task, suggesting increased spatial short-term memory, but has no effect on shoal cohesion, locomotor profile or anxiety-like behavior. Overall, our data suggest that moderate ELS may be linked to adaptive flexibility which contributes to build resilience in adult zebrafish by improving short-term spatial memory performance.

animal behavior and cognition↗

bioRxiv2020

A Test of Memory: The Fish, The Mouse, The Fly And The Human

Simple mazes have provided numerous tasks for assessing working memory. The discrete nature of choices in the T-maze has provided a robust protocol with sensitivity to cognitive deficits, whilst the continuous Y-maze reduces manual handling and pre-trial training. We have combined these attributes to develop a new behavioural task for assessing working memory, the Free-movement pattern (FMP) Y-maze. Using sequentially recorded left and right turns we demonstrate that zebrafish and mice use a single dominant strategy predominantly consisting of alternations between left and right choices trial-to-trial. We further tested this protocol with Drosophila and discovered an alternative invertebrate search strategy. Finally, a virtual human FMP Y-maze confirmed a common strategy among all tested vertebrate species, validating the translational power of the task for human research. The FMP Y-maze combines robust investigation of working memory and high translational power, generating a simple task with far-reaching impact.

animal behavior and cognition↗

bioRxiv2019

Zebrafish (Danio rerio) behavioral laterality predicts increased short-term avoidance memory but not stress-reactivity responses

Once considered a uniquely human attribute, behavioral laterality has proven to be ubiquitous among non{square}human animals, being frequently associated with different neurophenotypes in rodents and fish species. Zebrafish (Danio rerio) are a versatile and complementary vertebrate model system that has been widely used in translational neuropsychiatric research due their highly conserved genetic homology, well characterized physiological and extensive behavioral repertoire. Although the spontaneous left- and right-bias responses and associated behavioral domains (e.g. stress reactivity, aggression and learning) have previously been observed in other teleost species, no information regarding the natural left-right bias responses of zebrafish has been described. Thus, we aimed to investigate the existence and incidence of natural left-right bias of adult zebrafish in the Y-maze test and explore any relationship of biasedness on the performance of different behavioral domains. This included learning about threat-cues in the fear conditioning test and locomotion and anxiety-related behavior in the novel tank diving test. In conclusion, we showed for the first time that zebrafish exhibit a natural manifestation of behavioral lateralization which can influence aversive learning responses. Although laterality did not change locomotion or anxiety-related behaviors, we found that biased animals showed a reduction of short-term memory performance in the Y-maze and increase learning associated to fear cues.

animal behavior and cognition↗

bioRxiv2018

Moderate developmental alcohol exposure reduces repetitive alternation in a zebrafish model of fetal alcohol spectrum disorders.

The damaging effects of alcohol on a developing fetus are well known and cause a range of conditions known as fetal alcohol spectrum disorder (FASD). High levels of alcohol exposure lead to physical deformity and severe cognitive deficits, but more moderate exposure leads to a range of subtle cognitive effects such as reduced social behavior, higher propensity to develop addictions, and reduced spatial working memory. Previous studies have demonstrated that following exposure to relatively low levels of ethanol during early brain development (equivalent in humans to moderate exposure) zebrafish display a range of social and behavioral differences. Here, our aim was to test the hypothesis that moderate developmental ethanol exposure would affect aspects of learning and memory in zebrafish. In order to do this, we exposed zebrafish embryos to 20mM [0.12% v/v] ethanol from 2 to 9 dpf to model the effects of moderate prenatal ethanol (MPE) exposure. At 3 months old, adult fish were tested for appetitive and aversive learning, and for spatial alternation in a novel unconditioned y-maze protocol. We found that MPE did not affect appetitive or aversive learning, but exposed-fish showed a robust reduction in repetitive alternations in the y-maze when compared to age matched controls. This study confirms that moderate levels of ethanol exposure to developing embryos have subtle effects on spatial working memory in adulthood. Our data thus suggest that zebrafish may be a promising model system for studying the effects of alcohol on learning and decision-making, but also for developing treatments and interventions to reduce the negative effects of prenatal alcohol.

pharmacology and toxicology↗