The Role of Retinoic Acid in the Formation and Modulation of Invertebrate Electrical Synapses

Abstract

Communication between cells in the nervous system is dependent upon structures known as synapses. Synapses are broadly characterized as either chemical or electrical in nature, owing to the type of signals that are transmitted across them. Factors that can affect chemical synapses have been extensively studied. However, the factors that can influence the formation and modulation of electrical synapses are poorly understood. Retinoic acid, a vitamin A metabolite, is a known regulator of chemical synapses, yet its capacity to regulate electrical synapses is not as well established. Preliminary evidence from the central neurons of both invertebrates and vertebrates suggests that it is also capable of regulating the strength of electrical synapses. In this study, I provide further insights into how retinoic acid can act as a neuromodulator of electrical synapses. My findings suggest that retinoic acid is capable of rapidly altering the strength of electrical synapses in a dose- and isomer-dependent manner. Further, I provide evidence that this acute effect might be independent of either the retinoid receptors or a protein kinase. In addition, I provide novel findings to suggest retinoic acid is also capable of regulating the formation of electrical synapses. Long term exposure to two isomers of retinoic acid, all-trans-retinoic acid and 9-cis-retinoic acid, reduces both the proportion of cell pairs, and the average synaptic strength between cells that form electrical synapses. In summary, these investigations provide novel insights into the role that retinoids play in the both the formation and modulation of electrical synapses in the CNS.