Synaptic retinoic acid signaling and homeostatic synaptic plasticity

Neuropharmacology. 2014 Mar:78:3-12. doi: 10.1016/j.neuropharm.2012.12.004. Epub 2012 Dec 25.


One of the defining features of the nervous system is its ability to modify synaptic strength in an experience-dependent manner. Chronic elevation or reduction of network activity activates compensatory mechanisms that modulate synaptic strength in the opposite direction (i.e. reduced network activity leads to increased synaptic strength), a process called homeostatic synaptic plasticity. Among the many mechanisms that mediate homeostatic synaptic plasticity, retinoic acid (RA) has emerged as a novel signaling molecule that is critically involved in homeostatic synaptic plasticity induced by blockade of synaptic activity. In neurons, silencing of synaptic transmission triggers RA synthesis. RA then acts at synapses by a non-genomic mechanism that is independent of its well-known function as a transcriptional regulator, but operates through direct activation of protein translation in neuronal dendrites. Protein synthesis is activated by RA-binding to its receptor RARα, which functions locally in dendrites in a non-canonical manner as an RNA-binding protein that mediate RA's effect on translation. The present review will discuss recent progress in our understanding of the novel role of RA, which led to the identification of RA as a critical synaptic signaling molecule that mediates activity-dependent regulation of protein synthesis in neuronal dendrites. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.

Keywords: Fragile-X syndrome; Homeostatic synaptic plasticity; Local protein synthesis; Retinoic acid; Retinoic acid receptor α; Synaptic scaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Child Development Disorders, Pervasive / metabolism
  • Homeostasis
  • Humans
  • Intellectual Disability / metabolism
  • Neuronal Plasticity*
  • Receptors, Retinoic Acid / metabolism
  • Retinoic Acid Receptor alpha
  • Synapses / metabolism*
  • Tretinoin / metabolism*


  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Tretinoin