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Conserved serotonergic background of experience-dependent challenge-responding in zebrafish (Danio rerio).

bioRxiv, ISSN: 2692-8205
2019
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Article Description

Forming effective responses to threatening stimuli requires the adequate and coordinated emergence of stress-related internal states. Such ability depends on early-life experiences and, in connection, the adequate formation of neuromodulatory systems, particularly serotonergic signaling. Here, we assess the serotonergic background of experience-dependent behavioral responsiveness employing a zebrafish (Danio rerio) model. For the first time, we have characterized a period during the behavioral metamorphosis in which zebrafish are highly reactive to their environment. Absence of social stimuli during this phase established by isolated rearing fundamentally altered the behavioral phenotype of post-metamorphic zebrafish in a challenge-specific manner, partially due to a decline in responsiveness and an inability to develop stress-associated arousal state. In line with this, isolation differently affected whole-brain 5-HT signaling in resting and stress-induced conditions, an effect that was present at the level of the dorsal pallium and was negatively associated with responsiveness. Administration of the 5HT1AR partial agonist buspirone prevented the isolation-induced serotonin response to novelty in the forebrain and rescued stress-induced arousal along with challenge-induced behaviors, which altogether indicates a functional connection between these changes. In summary, there is a consistent negative association between behavioral responsiveness and serotonergic signaling in zebrafish, which is well recognizable through the modifying effects of developmental perturbation and pharmacological manipulations as well. Our results imply a conserved serotonergic mechanism that context-dependently modulates environmental reactivity and is highly sensitive to experiences acquired during a specific early-life time-window, a phenomenon that was previously only suggested in mammals.

Bibliographic Details

Varga, Zoltán K; Pejtsik, Diána; Biró, László; Zsigmond, Áron; Varga, Máté; Tóth, Blanka; Salamon, Vilmos; Annus, Tamás; Mikics, Éva; Aliczki, Manó

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

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