Research: Neurodevelopmental disorders
The problem
The fish cerebellum looks uniform, without the folds of the human cerebellum, yet its circuits are largely similar. Vestibulo- and spinocerebellum are better mapped in humans than cerebellar roles in higher functions such as social behavior. Autism-like changes in sociability are often thought uniquely human, but they are rooted in conserved brain function and sensory processing.
What we found — brain maps
We mapped zebrafish cerebellar efferents, imaged activity during swimming and nystagmus, and showed that anatomical maps match activity maps. Optogenetic intervention produced corresponding behavioral abnormalities. The work was published in PNAS in 2014.
Paper: Matsui et al., Proc. Natl. Acad. Sci. USA, 2014. doi:10.1073/pnas.1403105111
What we found — autism models and environment
In zebrafish lacking UBE3A, related to Angelman syndrome and ASD, we asked how social behavior depends on environment. In an anxiety-inducing white polystyrene tank, mutants stayed away from conspecifics; in a transparent acrylic tank resembling a breeding tank, social behavior improved. Gene expression and brain-activity mapping pointed to abnormal visual processing and heightened anxiety. Sociability in genetically predisposed individuals can be strongly modified by context (Dougnon and Matsui, Molecular Psychiatry, 2025). doi:10.1038/s41380-025-03180-0 / Press release
Link to human neurodevelopmental disorders
We are testing how cerebellar regions that interact with the cerebrum, in fish and humans, relate to developmental conditions, aiming at a deeper understanding of autism and ADHD.
Questions to take forward.
Neurodevelopmental disorders
Question How do genes and environment shape neuropsychiatric developmental disorders?
What we have found Cerebellar output in zebrafish is functionally regionalized (PNAS, 2014). The journal published a Commentary by editorial board member Hitoshi Okamoto. In ube3a mutant fish, sociability falls in an anxiety-inducing tank and recovers in a familiar one (Molecular Psychiatry, 2025).
What we want to ask next
- Long seen as a motor centre, how does the cerebellum take part in sociability and the mind? And what makes a better society?
- Why does sociability change with the environment, even with the same gene mutation?
Approaches We combine behavioural assays in small fishes with calcium imaging and genetic models. Circuit questions are tested with activity mapping or optogenetics; molecular questions connect to gene-expression analysis.
Who might start here A fit if you are interested in developmental disorders, social behaviour, the cerebellum or sensory processing. You can enter through behaviour or through imaging.
- Dougnon, G., Matsui, H.*. Environmental context modulates sociability in ube3a zebrafish mutants via alterations in sensory pathways. Mol. Psychiatry. 2025. doi:10.1038/s41380-025-03180-0
- Matsui, H.*, Namikawa, K., Babaryka, A. and Köster, R. Functional regionalization of the teleost cerebellum analyzed in vivo. Proc. Natl. Acad. Sci. USA. 2014. doi:10.1073/pnas.1403105111
Discuss research opportunities
Projects develop through discussion, starting from the lab’s research strengths and your interests and experience. We value researchers who learn from their results, refine the question and help shape the direction of their work.