title: MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets.
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.
authors.affiliation: Department of Neuroscience, University of Torino, 10125 Torino, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Fiumara
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032, USA.
authors.forename: Priyamvada
authors.initials: P
authors.lastname: Rajasethupathy
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Antonov
authors.affiliation: 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.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kosmidis
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Sossin
authors.affiliation: 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.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D000818:Animals; D001048:Aplysia / Q000502:physiology*; D001665:Binding Sites; D017774:Long-Term Potentiation / Q000235:genetics; D008568:Memory / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012701:Serotonin