The role of retinoic acid in the formation and modulation of invertebrate central synapses

J Neurophysiol. 2017 Feb 1;117(2):692-704. doi: 10.1152/jn.00737.2016. Epub 2016 Nov 16.


Trophic factors can influence many aspects of nervous system function, such as neurite outgrowth, synapse formation, and synapse modulation. The vitamin A metabolite, retinoic acid, can exert trophic effects to promote neuronal survival and outgrowth in many species and is also known to modulate vertebrate hippocampal synapses. However, its role in synaptogenesis has not been well studied, and whether it can modulate existing invertebrate synapses is also not known. In this study, we first examined a potential trophic effect of retinoic acid on the formation of excitatory synapses, independently of its role in neurite outgrowth, using cultured neurons of the mollusc Lymnaea stagnalis We also investigated its role in modulating both chemical and electrical synapses between various Lymnaea neurons in cell culture. Although we found no evidence to suggest retinoic acid affected short-term synaptic plasticity in the form of post-tetanic potentiation, we did find a significant cell type-specific modulation of electrical synapses. Given the prevalence of electrical synapses in invertebrate nervous systems, these findings highlight the potential for retinoic acid to modulate network function in the central nervous system of at least some invertebrates.

New & noteworthy: This study performed the first electrophysiological analysis of the ability of the vitamin A metabolite, retinoic acid, to exert trophic influences during synaptogenesis independently of its effects in supporting neurite outgrowth. It was also the first study to examine the ability of retinoic acid to modify both chemical and electrical synapses in any invertebrate, nonchordate species. We provide evidence that all-trans retinoic acid can modify invertebrate electrical synapses of central neurons in a cell-specific manner.

Keywords: electrical synapse; post-tetanic potentiation; synaptogenesis; trophic factor; vitamin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cells, Cultured
  • Central Nervous System / cytology*
  • Central Nervous System Depressants / pharmacology
  • Electrical Synapses / drug effects*
  • Electrophysiology
  • Ethanol / pharmacology
  • Lymnaea
  • Neuronal Plasticity / drug effects*
  • Neurons / classification
  • Neurons / drug effects*
  • Time Factors
  • Tretinoin / pharmacology*


  • Antineoplastic Agents
  • Central Nervous System Depressants
  • Ethanol
  • Tretinoin