Fever Induces Long-Term Synaptic Enhancement and Protects Learning in an Accelerated Aging Model

The physiological impact of fever on the brain remains poorly understood. Here, we demonstrate that temperature increases by yeast injection in rats (N=9) and by whole-body hyperthermia in mice (N=7) triggers structural synaptic enhancement in the prefrontal cortex through a mechanism involving AMPA-type glutamate receptors and protein translation (N=6). Repeated pyrexia induction in juvenile rats (N=9) results in synaptic strengthening that persists into adulthood, mitigating learning deficits and synaptic loss in a D-galactose model of accelerated aging (N=9-11). Our results show how common environmental conditions may shape brain function in the long-term via synaptic plasticity, warranting further exploration of thermal treatment for cognitive protection in aging.