The Zebrafish Cerebellar Neural Circuits Are Involved in Orienting Behavior

eNeuro. 2024 Oct 29;11(10):ENEURO.0141-24.2024. doi: 10.1523/ENEURO.0141-24.2024. Print 2024 Oct.

Abstract

Deficits in social behavior are found in neurodevelopmental disorders, including autism spectrum disorders (ASDs). Since abnormalities in cerebellar morphology and function are observed in ASD patients, the cerebellum is thought to play a role in social behavior. However, it remains unknown whether the cerebellum is involved in social behavior in other animals and how cerebellar circuits control social behavior. To address this issue, we employed zebrafish stereotyped orienting behavior as a model of social behaviors, in which a pair of adult zebrafish in two separate tanks approach each other, with one swimming at synchronized angles (orienting angles) with the other. We harnessed transgenic zebrafish that express botulinum toxin, which inhibits the release of neurotransmitters, in either granule cells or Purkinje cells (PCs), and zebrafish mutants of reelin, which is involved in the positioning of cerebellar neurons, including PCs. These zebrafish, deficient in the function or formation of cerebellar neural circuits, showed a significantly shorter period of orienting behavior compared with their control siblings. We found an increase in c-fos and egr1 expression in the cerebellum after the orienting behavior. These results suggest that zebrafish cerebellar circuits play an important role in social orienting behavior.

Keywords: autism spectrum disorders; cerebellum; orienting behavior; social behavior; zebrafish.

MeSH terms

  • Animals
  • Animals, Genetically Modified*
  • Behavior, Animal / physiology
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cerebellum* / metabolism
  • Cerebellum* / physiology
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / physiology
  • Neurons / metabolism
  • Neurons / physiology
  • Orientation / physiology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Reelin Protein*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Social Behavior*
  • Swimming / physiology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish*

Substances

  • Reelin Protein
  • Cell Adhesion Molecules, Neuronal
  • Serine Endopeptidases
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Zebrafish Proteins
  • Early Growth Response Protein 1
  • Proto-Oncogene Proteins c-fos