From knockout to natural variation: Investigating the role of BDNF in teleost behaviour and cognition

Brain Derived Neurotrophic Factor, is a highly conserved protein across vertebrate evolution, fundamental in neurophysiological processes such as neural growth, survival, and synaptic plasticity. This research overcame the major limitation of BDNF mammalian research (i.e., the perinatal lethality associated with a complete knockout) by utilizing teleost fish as translational models. Specifically, we exploited a viable CRISPR-Cas generated bdnf-knockout zebrafish to characterize its function in the complete absence of the protein. Studies in zebrafish showed that BDNF has a role in visual and motor lateralization, and that knockout larvae exhibit reduced recognition memory in the Novel Object Recognition test. Furthermore, BDNF was found to mediate the effects of environmental enrichment on behavior and cognitive plasticity during development. To explore BDNF natural variation, this research also used the Medaka Inbred Kiyosu-Karlsruhe panel to link naturally occurring genetic variation in bdnf expression levels to specific behavioral phenotypes. Overall, by combining a knockout model with a genetic variation model, this work confirmed BDNF's significant impact on teleost fish behavior and cognition, revealing functional homologies with mammals and advancing the use of these models in neuroscience.