fmr1 Mutation Alters the Early Development of Sensory Coding and Hunting and Social Behaviors in Larval Zebrafish

• Published in: The Journal of neuroscience Vol. 43; no. 7; pp. 1211 - 1224
• Main Authors: Zhu, Shuyu I, McCullough, Michael H, Pujic, Zac, Sibberas, Jordan, Sun, Biao, Darveniza, Thomas, Bucknall, Bianca, Avitan, Lilach, Goodhill, Geoffrey J
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 15-02-2023
• Subjects: Animals; Anxiety; Autism; Behavior; Coding; Danio rerio; Disease Models, Animal; Excitability; FMR1 protein; Fragile X Mental Retardation Protein - genetics; Fragile X syndrome; Fragile X Syndrome - genetics; Genotypes; Hunting; Hyperactivity; Hypersensitivity; Information processing; Intellectual disabilities; Larva - metabolism; Larvae; Mice; Mice, Knockout; Mutation; Mutation - genetics; Predatory behavior; Prey; RNA-Binding Proteins - genetics; Sensory integration; Sensory stimulation; Social Behavior; Social factors; Tectum; Vertebrates; Visual stimuli; Zebrafish; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; environmental enrichment; optic tectum; behavior; neural assemblies
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1721-22.2022

Autism spectrum disorders (ASDs) are developmental in origin; however, little is known about how they affect the early development of behavior and sensory coding. The most common inherited form of autism is Fragile X syndrome (FXS), caused by a mutation in
Mutation of
in zebrafish causes anxiety-like behavior, hyperactivity, and hypersensitivity in auditory and visual processing. Here, we show that zebrafish
-/- mutant larvae of either sex also display changes in hunting behavior, tectal coding, and social interaction. During hunting, they were less successful at catching prey and displayed altered behavioral sequences. In the tectum, representations of prey-like stimuli were more diffuse and had higher dimensionality. In a social behavioral assay, they spent more time observing a conspecific but responded more slowly to social cues. However, when given a choice of rearing environment
-/- larvae preferred one with reduced visual stimulation, and rearing them in this environment reduced genotype-specific effects on tectal excitability. Together, these results shed new light on how
-/- changes the early development of neural systems and behavior in a vertebrate.
Autism spectrum disorders (ASDs) are caused by changes in early neural development. Animal models of ASDs offer the opportunity to study these developmental processes in greater detail than in humans. Here, we found that a zebrafish mutant for a gene which in humans causes one type of ASD showed early alterations in hunting behavior, social behavior, and how visual stimuli are represented in the brain. However, we also found that mutant fish preferred reduced visual stimulation, and rearing them in this environment reduced alterations in neural activity patterns. These results suggest interesting new directions for using zebrafish as a model to study the development of brain and behavior in ASDs, and how the impact of ASDs could potentially be reduced.