Retinoic acid reduces the formation of, and acutely modulates, invertebrate electrical synapses

J Neurophysiol. 2024 Apr 3. doi: 10.1152/jn.00057.2024. Online ahead of print.

Abstract

Communication between cells in the nervous system is dependent on both chemical and electrical synapses. Factors that can affect chemical synapses have been well studied, but less is known about factors that influence electrical synapses. Retinoic acid, the Vitamin A metabolite, is a known regulator of chemical synapses, but few studies have examined its capacity to regulate electrical synapses. In this study, we determine that retinoic acid is capable of rapidly altering the strength of electrical synapses in an isomer and cell-dependent manner. Furthermore, we provide evidence that this acute effect might be independent of either the retinoid receptors or activation of a protein kinase. In addition to rapid modulatory effects of retinoic acid, we provide data to suggest that retinoic acid is also capable of regulating the formation of electrical synapses. Long-term exposure to both all-trans-retinoic acid or 9-cis-retinoic acid, reduced the proportion of cell pairs forming electrical synapses, as well as reduced the strength of electrical synapses that did form. In summary, this study provides insights into the role that retinoids might play in both the formation and modulation of electrical synapses in the CNS.

Keywords: Lymnaea stagnalis; gap junctions; innexins; non-genomic; retinoids.