Exercise‐augmentation of fear extinction depends on mTOR signaling

Abstract

Exercise has beneficial effects on cognition and mental health, such as enhancing the extinction of a traumatic memory. Rats allowed to run in a wheel for a single, two‐hour session immediately following fear extinction training show enhanced fear extinction memory. The mechanisms by which exercise augments fear extinction are unknown. The mammalian target of rapamycin (mTOR) is a translation regulator involved in synaptic plasticity, and is a target of cellular signals sensitive to exercise. Chronic exercise increases mTOR signaling in brain regions involved in extinction learning, but whether a single bout of exercise capable of enhancing fear extinction increases mTOR is also unknown. The goal of this study was to determine if a single session of wheel running increases mTOR signaling and, if so, whether mTOR signaling contributes to the exercise‐augmentation of fear extinction. Adult, male Long Evans rats exposed to auditory fear conditioning received intracerebral‐ventricular injections of the mTOR inhibitor rapamycin prior to fear extinction training. Immediately after fear extinction training, rats were placed in locked or mobile running wheel for two hours. Post‐extinction exercise enhanced fear extinction memory retrieval the following day, and this effect was blocked by rapamycin.Moreover, an acute bout of exercise increased mTOR signaling in several regions involved in memory and fear extinction. The increase in mTOR signaling produced by exercise was also blocked by rapamycin. These data suggest that acute exercise enhances fear extinction through a mechanism involving mTOR signaling.Support or Funding InformationSupported by the Undergraduate Research Opportunity Program, 2 T34 GM096958‐06, and NIH MH114992This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.