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PMID: 19778509 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB.

Neuron ·Vol. 63 ·No. 6 ·2009-09-24 ·Pages 803-17

Rajasethupathy P, Fiumara F, Sheridan R, Betel D, Puthanveettil SV, Russo JJ, Sander C, Tuschl T, Kandel E

Abstract

Memory storage and memory-related synaptic plasticity rely on precise spatiotemporal regulation of gene expression. To explore the role of small regulatory RNAs in learning-related synaptic plasticity, we carried out massive parallel sequencing to profile the small RNAs of Aplysia californica. We identified 170 distinct miRNAs, 13 of which were novel and specific to Aplysia. Nine miRNAs were brain enriched, and several of these were rapidly downregulated by transient exposure to serotonin, a modulatory neurotransmitter released during learning. Further characterization of the brain-enriched miRNAs revealed that miR-124, the most abundant and well-conserved brain-specific miRNA, was exclusively present presynaptically in a sensory-motor synapse where it constrains serotonin-induced synaptic facilitation through regulation of the transcriptional factor CREB. We therefore present direct evidence that a modulatory neurotransmitter important for learning can regulate the levels of small RNAs and present a role for miR-124 in long-term plasticity of synapses in the mature nervous system.

MeSH Terms
Analysis of Variance Animals Aplysia/physiology Central Nervous System/cytology,drug effects,physiology Cyclic AMP Response Element-Binding Protein/metabolism Dose-Response Relationship, Drug Enzyme Inhibitors/pharmacology Evolution, Molecular Excitatory Postsynaptic Potentials/drug effects,genetics Kinesins/metabolism MicroRNAs/antagonists & inhibitors,physiology Molecular Biology/methods Mutation/physiology Nerve Tissue Proteins/metabolism Neuronal Plasticity/drug effects,genetics,physiology Neurons/drug effects,physiology Oligonucleotides, Antisense/pharmacology Protein Binding/drug effects Serotonin/pharmacology Synapses/drug effects,physiology Time Factors Ubiquitin Thiolesterase/metabolism
Chemicals
Cyclic AMP Response Element-Binding Protein Enzyme Inhibitors MicroRNAs Nerve Tissue Proteins Oligonucleotides, Antisense Serotonin Ubiquitin Thiolesterase Kinesins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Rajasethupathy Priyamvada
Department of Neuroscience, Columbia University, New York, NY 10032, USA.
Fiumara Ferdinando
Sheridan Robert
Betel Doron
Puthanveettil Sathyanarayanan V
Russo James J
Sander Chris
Tuschl Thomas
Kandel Eric
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2009.05.029
Published
2009-09-24
Pages
803-17
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2875683
Subset
IM
Grants
NIMH NIH HHS · R01 MH075026-05 · United States
NIMH NIH HHS · F30 MH086267 · United States
NINDS NIH HHS · R01 NS060762 · United States
NHGRI NIH HHS · P50 HG002806 · United States
NIGMS NIH HHS · P01 GM073047 · United States
NIGMS NIH HHS · P01 GM073047-050001 · United States
NIMH NIH HHS · R01 MH075026 · United States
Howard Hughes Medical Institute · United States
Corrections
CommentIn
PMID: 19778498
External Links
PubMed source DOI: 10.1016/j.neuron.2009.05.029 PMC Full Text View journal details
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