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.
Highlights
20 The beneficial cognitive effects of physical exercise cross the lifespan as well as disease boundaries [1, 2]
These results indicate that dentate granule cells activated by a single bout of exercise show a laminar-specific increase in dendritic spines and in excitatory postsynaptic currents
Our experiments were designed to test the cellular and molecular response to acute 10 exercise with an emphasis on time periods during which synapses might form or reorganize. This approach differs from studies of sustained or chronic exercise that likely involve systemic as well as neural mechanisms [3, 4, 26]
Summary
20 The beneficial cognitive effects of physical exercise cross the lifespan as well as disease boundaries [1, 2]. The dentate gyrus is uniquely important in learning and memory, acting as an input stage for encoding contextual and spatial information from multiple brain regions This circuit is well suited to its biological function because of its sparse coding design, with only a few dentate granule cells active at any one time [5,6,7]. These properties provide an ideal network to investigate how exercise-induced 5 changes in activity-dependent gene expression affect hippocampal structural and synaptic plasticity in vivo. The increase in Fos expression, assessed by immunohistochemistry, matched the increase in TdTomatoaCC-BY-NC-ND 4.0 International license
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