Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L

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.

Hypothesized Mechanisms Through Which Exercise May Attenuate Memory Interference

“…Acute exercise also increases cerebral blood flow, neural activity, and receptor activity, which may lead to increased neuroplasticity [15], and ultimately, enhanced memory function. Recent work demonstrates that acute exercise may induce neuroplasticity via I-BAR gene expression [28].…”

Recruitment of parvalbumin and somatostatin interneuron inputs to adult born dentate granule neurons

“…Interestingly we found no effect of running on GABA input to mature cells. A recent study used a Fos-Trap approach to identify mature granule cells that are active during a single 2-h bout of running and found considerable plasticity of their excitatory inputs from the entorhinal cortex 49 . In our analysis we were not able to specifically identify DGCs that might have been active during long term running, but it is possible that PV and SST inputs might be differentially modulated in active DGCs compared to the total population.…”

Protective actions of exercise‐related FNDC5/Irisin in memory and Alzheimer’s disease

“…Interestingly, some of these effects have been associated with exercise-induced adult hippocampal neurogenesis (Klempin et al, 2013;Xu, 2013). Accordingly, voluntary running stimulates the rewiring of neurons in the entorhinal cortex (Voss et al, 2019) and promotes synapse formation and function, possibly through the activity of the transcription factor metastasis-suppressor 1-like (Mtss1L) in the dentate gyrus (Chatzi et al, 2019). Taken together, these findings indicate that physical exercise promotes several signaling mechanisms to maintain healthy cells and networks in the brain.…”