Retinoic acid induces changes in electrical properties of adult neurons in a dose- and isomer-dependent manner

The electrical activity of neurons is known to play a role in neuronal development, as well as repair of adult nervous tissue. For example, the extension of neurites and motility of growth cones can be modulated by changes in the electrical firing of neurons. The vitamin A metabolite retinoic acid also plays a critical role during nervous system development and is also known to elicit regenerative responses, namely the induction, enhancement, and directionality of neurite outgrowth. However, no studies have previously reported the ability of retinoic acid to modify the electrical activity of neurons. In this study, we determined whether retinoic acid might exert effects on the nervous system by altering the electrical properties of neurons. Using cultured adult neurons from Lymnaea stagnalis, we showed that acute application of retinoic acid can rapidly elicit changes in neuronal firing properties. Retinoic acid caused the presence of atypical firing behavior such as rhythmic bursting and altered the shape of action potentials, causing increases in half-amplitude duration and decay time. Retinoic acid also caused cell silencing, whereby neuronal activity was halted within an hour. These effects of retinoic acid were shown to be both dose and isomer dependent. We then showed that the effects of retinoic acid on cell firing (but not silencing) were significantly reduced in the presence of an retinoid X receptor pan-antagonist HX531. This study suggests that some of the effects of retinoic acid during neuronal development or regeneration might possibly occur as a result of changes in electrical activity of neurons.