Agrin plays an organizing role in the formation of sympathetic synapses

Jacinthe Gingras, Siamak Rassadi, Ellis Cooper, Michael J Ferns

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Agrin is a nerve-derived factor that directs neuromuscular synapse formation, however its role in regulating interneuronal synaptogenesis is less clear. Here, we examine agrin's role in synapse formation between cholinergic preganglionic axons and sympathetic neurons in the superior cervical ganglion (SCG) using agrin-deficient mice. In dissociated cultures of SCG neurons, we found a significant decrease in the number of synapses with aggregates of presynaptic synaptophysin and postsynaptic neuronal acetylcholine receptor among agrin-deficient neurons as compared to wild-type neurons. Moreover, the levels of pre- and postsynaptic markers at the residual synapses in agrin-deficient SCG cultures were also reduced, and these defects were rescued by adding recombinant neural agrin to the cultures. Similarly, we observed a decreased matching of pre- and postsynaptic markers in SCG of agrin-deficient embryos, reflecting a decrease in the number of differentiated synapses in vivo. Finally, in electrophysiological experiments, we found that paired-pulse depression was more pronounced and posttetanic potentiation was significantly greater in agrin-deficient ganglia, indicating that synaptic transmission is also defective. Together, these findings indicate that neural agrin plays an organizing role in the formation and/or differentiation of interneuronal, cholinergic synapses.

Original languageEnglish (US)
Pages (from-to)1109-1118
Number of pages10
JournalJournal of Cell Biology
Volume158
Issue number6
DOIs
StatePublished - Sep 16 2002
Externally publishedYes

Keywords

  • Agrin knockout
  • Compound action potential
  • Neuronal acetylcholine receptors
  • Superior cervical ganglia
  • Synaptogenesis

ASJC Scopus subject areas

  • Cell Biology

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