Document Type
Article
Publication Date
8-25-2024
Original Citation
Joy M,
Carmichael S.
Activity-dependent transcriptional programs in memory regulate motor recovery after stroke. Commun Biol. 2024;7(1):1048.
Keywords
JMG, Animals, Stroke, Mice, Recovery of Function, Memory, Neuronal Plasticity, Male, Disease Models, Animal, Microglia, Neurons, Mice, Inbred C57BL, Gene Regulatory Networks, Transcription, Genetic, Motor Activity
JAX Source
Commun Biol. 2024;7(1):1048.
ISSN
2399-3642
PMID
39183218
DOI
https://doi.org/10.1038/s42003-024-06723-3
Grant
These studies were funded by Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (S.T.C) and JAX—institutional start-up funds (M.T.J.).
Abstract
Stroke causes death of brain tissue leading to long-term deficits. Behavioral evidence from neurorehabilitative therapies suggest learning-induced neuroplasticity can lead to beneficial outcomes. However, molecular and cellular mechanisms that link learning and stroke recovery are unknown. We show that in a mouse model of stroke, which exhibits enhanced recovery of function due to genetic perturbations of learning and memory genes, animals display activity-dependent transcriptional programs that are normally active during formation or storage of new memories. The expression of neuronal activity-dependent genes are predictive of recovery and occupy a molecular latent space unique to motor recovery. With motor recovery, networks of activity-dependent genes are co-expressed with their transcription factor targets forming gene regulatory networks that support activity-dependent transcription, that are normally diminished after stroke. Neuronal activity-dependent changes at the circuit level are influenced by interactions with microglia. At the molecular level, we show that enrichment of activity-dependent programs in neurons lead to transcriptional changes in microglia where they differentially interact to support intercellular signaling pathways for axon guidance, growth and synaptogenesis. Together, these studies identify activity-dependent transcriptional programs as a fundamental mechanism for neural repair post-stroke.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.