Abstract
Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines—tiny protrusions accommodating excitatory synapses. Both LTP and spine remodelling are crucial for brain development, cognition and the pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the maintenance of LTP, however, is not well understood. Using next-generation sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3. Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate ‘LTP miRNAs'.
Highlights
Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength
Long-term potentiation (LTP) of synaptic transmission is a form of synaptic plasticity that leads to long-lasting enhancement of synaptic strength
LTP was induced in hippocampal slices prepared from mice (2B3 weeks old) by tetanic stimulation of the Schaffer collateral pathway (4 trains of 100 Hz, 1 s stimulation separated by 5 min)[13,14,15,16]
Summary
Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines—tiny protrusions accommodating excitatory synapses. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate ‘LTP miRNAs’. Long-term potentiation (LTP) of synaptic transmission is a form of synaptic plasticity that leads to long-lasting enhancement of synaptic strength. Extracellular signal-regulated kinase and mammalian target of rapamycin play important roles in translational regulation in LTP They promote phosphorylation of proteins in the translational machinery to facilitate translation initiation, thereby enhancing protein synthesis[5]. The role of miRNAs in LTP, has yet to be determined
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