Fever induces long-term synaptic enhancement and protects learning in an accelerated aging model

Physiological impact of fever in the brain remains poorly understood. Here, we demonstrate that induction of fever by yeast injection in rats (N=9) and by whole-body hyperthermia in mice (N=7) triggers structural synaptic enhancement in the prefrontal cortex involving AMPA-type glutamate receptor signalling and protein translation (N=6). Repeated fever 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=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.