Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 19, Pages 9616-9621Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1819374116
Keywords
atomic force microscopy; force mapping; microRNAs; dendritic spines; structural plasticity
Categories
Funding
- National Research Foundation of Korea (NRF) - Korean government (Ministry of Science and ICT) [2017R1A2B3008478, 2015M3C7A1030964]
- NRF [2018R1A3B1052079, 2018M3C7A1024152, 2017R1A2B2004122]
- CREST from the Japan Science and Technology Agency (JST) [JPMJCR1652]
- World Premier International Research Center Initiative (WPI) from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
- National Research Foundation of Korea [2017R1A2B2004122, 2018M3C7A1024152, 2018R1A3B1052079, 2015M3C7A1030964, 2017R1A2B3008478] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Dendritic spines are major loci of excitatory inputs and undergo activity-dependent structural changes that contribute to synaptic plasticity and memory formation. Despite the existence of various classification types of spines, how they arise and which molecular components trigger their structural plasticity remain elusive. microRNAs (miRNAs) have emerged as critical regulators of synapse development and plasticity via their control of gene expression. Brain-specific miR-134s likely regulate the morphological maturation of spines, but their subcellular distributions and functional impacts have rarely been assessed. Here, we exploited atomic force microscopy to visualize in situ miR-134s, which indicated that they are mainly distributed at nearby dendritic shafts and necks of spines. The abundance of miR-134s varied between morphologically and functionally distinct spine types, and their amounts were inversely correlated with their postulated maturation stages. Moreover, spines exhibited reduced contents of miR-134s when selectively stimulated with beads containing brain-derived neurotropic factor (BDNF). Taken together, in situ visualizations of miRNAs provided unprecedented insights into the inverse synaptic-tagging roles of miR-134s that are selective to inactive/irrelevant synapses and potentially a molecular means for modifying synaptic connectivity via structural alteration.
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