Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L
- Oregon Health and Science University, United States
Abstract
Exercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked activated mature hippocampal dentate granule cells using conditional Fos-TRAP mice. Exercise-activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied I-BAR domain-containing gene, which we hypothesized could be involved in membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.
Data availability
RNA seq data generated in the manuscript have been deposited at https://www.ncbi.nlm.nih.gov/bioproject/PRJNA481775
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Brief Running Activated vs Non-activated Neurons RNAseqNCBI Bioproject, PRJNA481775.
Article and author information
Author details
Funding
National Institutes of Health (NS080979)
- Richard H Goodman
- Gary L Westbrook
U.S. Department of Defense (W81XWH-18-1-0598)
- Eric Schnell
U.S. Department of Veterans Affairs (I01-BX002949)
- Eric Schnell
Lawrence Ellison Foundation
- Richard H Goodman
National Institutes of Health (F31-NS098597)
- Wiiliam D Hendricks
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- John Huguenard, Stanford University School of Medicine, United States
Ethics
Animal experimentation: All procedures were performed according to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and were in compliance with approved IACUC protocols at Oregon Health & Science University (protocol# TR01-IP00000148). For surgeries, all mice were anesthetized using an isoflurane delivery system (Veterinary Anesthesia Systems Co.) by spontaneous respiration and every effort was made to minimize suffering.All investigators underwent institutional Responsible Conduct & Research training.
Version history
- Received: February 9, 2019
- Accepted: June 22, 2019
- Accepted Manuscript published: June 24, 2019 (version 1)
- Version of Record published: July 4, 2019 (version 2)
Copyright
© 2019, Chatzi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L
eLife 8:e45920.
https://doi.org/10.7554/eLife.45920
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