Synaptic Plasticity is Altered by Supraphysiological Levels of Retinoic Acid Acting Nongenomically however Endogenous Retinoic Acid Has Not Been Shown to Control Synaptic Plasticity

A paper recently published on forebrain cortical synaptic plasticity reports that retinoic acid (RA) induces synaptopodin-dependent metaplasticity in mouse dentate granule cells (Lenz et al., 2021). Retinoic acid (RA) is the active form of vitamin A that functions as a ligand for nuclear RA receptors that directly bind genomic control regions to regulate gene expression (Chambon, 1996; Ghyselinck and Duester, 2019). However, Lenz et al. report that RA functions in a nongenomic fashion to control forebrain cortical synaptic plasticity which modulates synaptic transmission to effectively respond to specific stimuli; specifically, they report that this nongenomic response occurs in the dorsal hippocampus but not ventral hippocampus. They performed RA treatment studies which provided information on how a supraphysiological level of RA effects synaptic plasticity. However, the authors did not perform an RA loss-of-function study to verify that endogenous RA is required for synaptic plasticity.