Excitatory synaptogenesis between identified Lymnaea neurons requires extrinsic trophic factors and is mediated by receptor tyrosine kinases

Toshiro Hamakawa, Melanie A. Woodin, Micki C. Bjorgum, Sherry D. Painter, Mayumi Takasaki, Ken Lukowiak, Gregg T. Nagle, Naweed I. Syed

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Neurotrophic factors have well established roles in neuronal development and adult synaptic plasticity, but their precise role in synapse formation has yet to be determined. This paper provides the first direct evidence that neurotrophic factors in brain conditioned medium (CM) differentially regulate excitatory and inhibitory synapse formation. Somata of identified presynaptic and postsynaptic neurons were isolated from the CNS of Lymnaea and were cultured in a soma-soma configuration in the presence (CM) or absence [defined medium (DM)] of trophic factors. In DM, excitatory synapses did not form. When they were paired in CM or in DM containing Lymnaea epidermal growth factor (EGF); however, all presynaptic neurons reestablished their specific excitatory synapses, which had electrical properties similar to those seen in vivo. CM-induced formation of excitatory synapses required transcription and de novo protein synthesis, as indicated by the observations that synapse formation was blocked by the protein synthesis inhibitor anisomycin and the protein transcription blocker actinomycin D; the CM factor was inactivated by boiling. They were also blocked by receptor tyrosine kinase inhibitors (lavendustin A, genistein, K252a, and KT5926) but not by inactive analogs (genistin and lavendustin B), suggesting that the effect was mediated by receptor tyrosine kinases. These results, together with our previously published data, demonstrate that trophic factors are required for excitatory, but not inhibitory, synapse formation and extends the role of EGF from cell proliferation, neurite outgrowth, and survival to excitatory synapse formation.

Original languageEnglish (US)
Pages (from-to)9306-9312
Number of pages7
JournalJournal of Neuroscience
Volume19
Issue number21
StatePublished - Nov 1 1999
Externally publishedYes

Fingerprint

Lymnaea
Receptor Protein-Tyrosine Kinases
Synapses
Neurons
Conditioned Culture Medium
Carisoprodol
Nerve Growth Factors
Epidermal Growth Factor
Anisomycin
Neuronal Plasticity
Protein Synthesis Inhibitors
Genistein
Dactinomycin
Proteins
Cell Proliferation
Brain

Keywords

  • EGF
  • Lymnaea
  • Protein synthesis
  • Soma-soma synapses
  • Synapse formation
  • Trk receptors
  • Trophic factors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hamakawa, T., Woodin, M. A., Bjorgum, M. C., Painter, S. D., Takasaki, M., Lukowiak, K., ... Syed, N. I. (1999). Excitatory synaptogenesis between identified Lymnaea neurons requires extrinsic trophic factors and is mediated by receptor tyrosine kinases. Journal of Neuroscience, 19(21), 9306-9312.

Excitatory synaptogenesis between identified Lymnaea neurons requires extrinsic trophic factors and is mediated by receptor tyrosine kinases. / Hamakawa, Toshiro; Woodin, Melanie A.; Bjorgum, Micki C.; Painter, Sherry D.; Takasaki, Mayumi; Lukowiak, Ken; Nagle, Gregg T.; Syed, Naweed I.

In: Journal of Neuroscience, Vol. 19, No. 21, 01.11.1999, p. 9306-9312.

Research output: Contribution to journalArticle

Hamakawa, T, Woodin, MA, Bjorgum, MC, Painter, SD, Takasaki, M, Lukowiak, K, Nagle, GT & Syed, NI 1999, 'Excitatory synaptogenesis between identified Lymnaea neurons requires extrinsic trophic factors and is mediated by receptor tyrosine kinases', Journal of Neuroscience, vol. 19, no. 21, pp. 9306-9312.
Hamakawa T, Woodin MA, Bjorgum MC, Painter SD, Takasaki M, Lukowiak K et al. Excitatory synaptogenesis between identified Lymnaea neurons requires extrinsic trophic factors and is mediated by receptor tyrosine kinases. Journal of Neuroscience. 1999 Nov 1;19(21):9306-9312.
Hamakawa, Toshiro ; Woodin, Melanie A. ; Bjorgum, Micki C. ; Painter, Sherry D. ; Takasaki, Mayumi ; Lukowiak, Ken ; Nagle, Gregg T. ; Syed, Naweed I. / Excitatory synaptogenesis between identified Lymnaea neurons requires extrinsic trophic factors and is mediated by receptor tyrosine kinases. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 21. pp. 9306-9312.
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