MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets

Cell Rep. 2015 Jun 30;11(12):1866-75. doi: 10.1016/j.celrep.2015.05.034. Epub 2015 Jun 18.


The maintenance phase of memory-related long-term facilitation (LTF) of synapses between sensory and motor neurons of the gill-withdrawal reflex of Aplysia depends on a serotonin (5-HT)-triggered presynaptic upregulation of CPEB, a functional prion that regulates local protein synthesis at the synapse. The mechanisms whereby serotonin regulates CPEB levels in presynaptic sensory neurons are not known. Here, we describe a sensory neuron-specific microRNA 22 (miR-22) that has multiple binding sites on the mRNA of CPEB and inhibits it in the basal state. Serotonin triggers MAPK/Erk-dependent downregulation of miR-22, thereby upregulating the expression of CPEB, which in turn regulates, through functional CPE elements, the presynaptic expression of atypical PKC (aPKC), another candidate regulator of memory maintenance. Our findings support a model in which the neurotransmitter-triggered downregulation of miR-22 coordinates the regulation of genes contributing synergistically to the long-term maintenance of memory-related synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aplysia / physiology*
  • Binding Sites
  • Long-Term Potentiation / genetics
  • Memory / physiology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Motor Neurons / metabolism
  • Motor Neurons / physiology
  • Neuronal Plasticity / genetics
  • Protein Biosynthesis
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Sensory Receptor Cells
  • Serotonin / genetics
  • Serotonin / metabolism*
  • Synapses / genetics
  • Synapses / metabolism


  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • Serotonin