- Keiser, Ashley;
- Dong, Tri;
- Kramár, Enikö;
- Butler, Christopher;
- Chen, Siwei;
- Matheos, Dina;
- Rounds, Jacob;
- Rodriguez, Alyssa;
- Beardwood, Joy;
- Augustynski, Agatha;
- Al-Shammari, Ameer;
- Alaghband, Yasaman;
- Alizo Vera, Vanessa;
- Berchtold, Nicole;
- Shanur, Sharmin;
- Cotman, Carl;
- Baldi, Pierre;
- Wood, Marcelo
Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.