Mir324 knockout regulates the structure of dendritic spines and impairs hippocampal long-term potentiation
Abstract MicroRNAs are an emerging class of synaptic regulators. These small noncoding RNAs post-transcriptionally regulate gene expression, thereby altering neuronal pathways and shaping cell-to-cell communication. Their ability to rapidly alter gene expression and target multiple pathways makes th...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-49134-w |
| _version_ | 1797388382010081280 |
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| author | Emma V. Parkins Darrin H. Brager Jeffrey K. Rymer John M. Burwinkel Diego Rojas Durgesh Tiwari Yueh-Chiang Hu Christina Gross |
| author_facet | Emma V. Parkins Darrin H. Brager Jeffrey K. Rymer John M. Burwinkel Diego Rojas Durgesh Tiwari Yueh-Chiang Hu Christina Gross |
| author_sort | Emma V. Parkins |
| collection | DOAJ |
| description | Abstract MicroRNAs are an emerging class of synaptic regulators. These small noncoding RNAs post-transcriptionally regulate gene expression, thereby altering neuronal pathways and shaping cell-to-cell communication. Their ability to rapidly alter gene expression and target multiple pathways makes them interesting candidates in the study of synaptic plasticity. Here, we demonstrate that the proconvulsive microRNA miR-324-5p regulates excitatory synapse structure and function in the hippocampus of mice. Both Mir324 knockout (KO) and miR-324-5p antagomir treatment significantly reduce dendritic spine density in the hippocampal CA1 subregion, and Mir324 KO, but not miR-324-5p antagomir treatment, shift dendritic spine morphology, reducing the proportion of thin, “unstable” spines. Western blot and quantitative Real-Time PCR revealed changes in protein and mRNA levels for potassium channels, cytoskeletal components, and synaptic markers, including MAP2 and Kv4.2, which are important for long-term potentiation (LTP). In line with these findings, slice electrophysiology revealed that LTP is severely impaired in Mir324 KO mice, while neurotransmitter release probability remains unchanged. Overall, this study demonstrates that miR-324-5p regulates dendritic spine density, morphology, and plasticity in the hippocampus, potentially via multiple cytoskeletal and synaptic modulators. |
| first_indexed | 2024-03-08T22:40:00Z |
| format | Article |
| id | doaj.art-07598c5410004486bbda98f3ddb1749f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T22:40:00Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-07598c5410004486bbda98f3ddb1749f2023-12-17T12:12:11ZengNature PortfolioScientific Reports2045-23222023-12-0113111410.1038/s41598-023-49134-wMir324 knockout regulates the structure of dendritic spines and impairs hippocampal long-term potentiationEmma V. Parkins0Darrin H. Brager1Jeffrey K. Rymer2John M. Burwinkel3Diego Rojas4Durgesh Tiwari5Yueh-Chiang Hu6Christina Gross7University of Cincinnati Neuroscience Graduate ProgramCenter for Learning and Memory, Department of Neuroscience, The University of Texas at AustinDivision of Neurology, Cincinnati Children’s Hospital Medical CenterDivision of Neurology, Cincinnati Children’s Hospital Medical CenterDivision of Neurology, Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati Neuroscience Graduate ProgramDepartment of Pediatrics, University of Cincinnati College of MedicineUniversity of Cincinnati Neuroscience Graduate ProgramAbstract MicroRNAs are an emerging class of synaptic regulators. These small noncoding RNAs post-transcriptionally regulate gene expression, thereby altering neuronal pathways and shaping cell-to-cell communication. Their ability to rapidly alter gene expression and target multiple pathways makes them interesting candidates in the study of synaptic plasticity. Here, we demonstrate that the proconvulsive microRNA miR-324-5p regulates excitatory synapse structure and function in the hippocampus of mice. Both Mir324 knockout (KO) and miR-324-5p antagomir treatment significantly reduce dendritic spine density in the hippocampal CA1 subregion, and Mir324 KO, but not miR-324-5p antagomir treatment, shift dendritic spine morphology, reducing the proportion of thin, “unstable” spines. Western blot and quantitative Real-Time PCR revealed changes in protein and mRNA levels for potassium channels, cytoskeletal components, and synaptic markers, including MAP2 and Kv4.2, which are important for long-term potentiation (LTP). In line with these findings, slice electrophysiology revealed that LTP is severely impaired in Mir324 KO mice, while neurotransmitter release probability remains unchanged. Overall, this study demonstrates that miR-324-5p regulates dendritic spine density, morphology, and plasticity in the hippocampus, potentially via multiple cytoskeletal and synaptic modulators.https://doi.org/10.1038/s41598-023-49134-w |
| spellingShingle | Emma V. Parkins Darrin H. Brager Jeffrey K. Rymer John M. Burwinkel Diego Rojas Durgesh Tiwari Yueh-Chiang Hu Christina Gross Mir324 knockout regulates the structure of dendritic spines and impairs hippocampal long-term potentiation Scientific Reports |
| title | Mir324 knockout regulates the structure of dendritic spines and impairs hippocampal long-term potentiation |
| title_full | Mir324 knockout regulates the structure of dendritic spines and impairs hippocampal long-term potentiation |
| title_fullStr | Mir324 knockout regulates the structure of dendritic spines and impairs hippocampal long-term potentiation |
| title_full_unstemmed | Mir324 knockout regulates the structure of dendritic spines and impairs hippocampal long-term potentiation |
| title_short | Mir324 knockout regulates the structure of dendritic spines and impairs hippocampal long-term potentiation |
| title_sort | mir324 knockout regulates the structure of dendritic spines and impairs hippocampal long term potentiation |
| url | https://doi.org/10.1038/s41598-023-49134-w |
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