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

Abstract

5Early-life stress (ELS) is defined as a short or chronic period of trauma, environmental or 3 6 social deprivation, which can affect different neurochemical and behavioral patterns during 3 7 adulthood. Zebrafish (Danio rerio) have been widely used as a model system to understand human 3 8 neurodevelopmental disorders and display translationally relevant behavioral and stress-regulating 3 9systems. In this study, we aimed to investigate the effects of moderate ELS by exposing young 4 0 animals (six weeks post-fertilization), for three consecutive days, to three stressors, and analyzing 4 1 the impact of this on adult zebrafish behavior (sixteen weeks post-fertilization). The ELS impact in 4 2 adults was assessed though analysis of performance on tests of unconditioned memory (free 4 3 movement pattern Y-maze test), exploratory and anxiety-related task (novel tank diving test) and 4 4 social cohesion (shoaling test). Here, we show for the first time that moderate ELS increases the 4 5 number of pure alternations compared to pure repetitions in the unconditioned Y-maze task, 4 6suggesting increased spatial short-term memory, but has no effect on shoal cohesion, locomotor 4 7 profile or anxiety-like behavior. Overall, our data suggest that moderate ELS may be linked to 4 8 adaptive flexibility which contributes to build 'resilience' in adult zebrafish by improving short-4 9 term spatial memory performance. 5 0 5 1

Early Mistreatment Contributes to Social Behavior Disorders in Zebrafish

“…Thus, we showed that stress caused in the development interval between 20 and 30 dpf did not cause changes in motor patterns. Our results agree with those by Fontana et al ( 2020 ) that used other stressors (water change, shallow water, and overcrowding) applied over 3 days at ~40 dpf. These authors found no effects of stress on locomotor and anxiety-related responses.…”

“…Early-life stress is known to affect neurochemical and behavioral patterns that lead to behavioral issues during adulthood. Some stressors imposed in moderate amounts contribute to increased behavioral flexibility and even improve cognitive performance (Fontana et al, 2020 ). However, some social stressors, such as the one imposed in this study, may trigger brain alterations that affect the proper behavioral repertoire and lead to psychological deficits.…”

“…In this sense, the zebrafish is the ideal compromise between the physiological (cortisol release instead of corticosterone) and behavioral responses, and the facility of breeding and manipulation avoids stress interference before the juvenile phase of development. In zebrafish, whose characteristics differ from mammals in terms of parental care, social structure, and types of intraspecific interactions, animals that experience stress in the juvenile phase do not exhibit anxiety-related behaviors in adulthood but show differences related to memory (Paull et al, 2010 ; Séguret et al, 2019 ; Fontana et al, 2020 ). However, new approaches need to be explored to better understand the long-term responses of zebrafish to disturbances in the early stages of development.…”

Lifelong molecular consequences of high Glucocorticoids exposure during development

“…In zebrafish, fear-conditioned avoidance learning is a robust phenotype whereby fish exhibit freezing and erratic behavior upon re-exposure to the conditioned stimulus (CS) 73,74 . Although one study found that chronic unpredictable stress did not have any effect on fear conditioning in adult zebrafish 75 , a different ELS protocol found improvement of short-term memory by early life stress when testing in the unconditioned y-maze 76 . Differences in how zebrafish learn fear association are dependent on whether they are reactive or proactive responders to stress, raising the question of how bPAC+ fish's response fits into that spectrum 77 .…”

Improving zebrafish laboratory welfare and scientific research through understanding their natural history

“…For example, intermittent crowding of adult zebrafish has been shown to increase cortisol secretion and reduce their capacity to renew heart tissue after injury (Sallin & Ja zwi nska, 2016), with ramifications for studies of stress responses and tissue regeneration. Temporary crowding has been reported to improve zebrafish working memory (Fontana et al, 2021) with implications for neurobiology, spatial learning and memory research. Further, crowding embryos may lead to hypoxia, which has been shown to result in a higher percentage of malformations and a male-biased F1 generation (Wu, 2009).…”