Late onset of Synaptotagmin 2a expression at synapses relevant to social behavior

J Comp Neurol. 2021 Jun;529(9):2176-2188. doi: 10.1002/cne.25084. Epub 2020 Dec 17.


As they form, synapses go through various stages of maturation and refinement. These steps are linked to significant changes in synaptic function, potentially resulting in emergence and maturation of behavioral outputs. Synaptotagmins are calcium-sensing proteins of the synaptic vesicle exocytosis machinery, and changes in Synaptotagmin proteins at synapses have significant effects on vesicle release and synaptic function. Here, we examined the distribution of the synaptic vesicle protein Synaptotagmin 2a (Syt2a) during development of the zebrafish nervous system. Syt2a is widely distributed throughout the midbrain and hindbrain early during larval development but very weakly expressed in the forebrain. Later in development, Syt2a expression levels in the forebrain increase, particularly in regions associated with social behavior, and most intriguingly, around the time social behavior becomes apparent. We provide evidence that Syt2a localizes to synapses onto neurons implicated in social behavior in the ventral forebrain and show that Syt2a is colocalized with tyrosine hydroxylase, a biosynthetic enzyme in the dopamine pathway. Our results suggest a developmentally important role for Syt2a in maturing synapses in the forebrain, coinciding with the emergence of social behavior.

Keywords: Synaptotagmin; social behavior; synapse; tyrosine hydroxylase; ventral forebrain; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Gene Expression
  • Prosencephalon / embryology
  • Prosencephalon / metabolism*
  • Social Behavior*
  • Synapses / genetics
  • Synapses / metabolism*
  • Synaptotagmin II / biosynthesis*
  • Synaptotagmin II / genetics
  • Zebrafish


  • Synaptotagmin II