Format

Send to

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

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

Author information

1
Department of Neuroscience, University of Torino, 10125 Torino, Italy.
2
Department of Neuroscience, Columbia University, New York, NY 10032, USA.
3
Department of Neuroscience, Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA.
4
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
5
Department of Neuroscience, Columbia University, New York, NY 10032, USA; Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA. Electronic address: erk5@columbia.edu.

Abstract

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.

PMID:
26095361
DOI:
10.1016/j.celrep.2015.05.034
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center