Site-Specific Regulation of Tau phosphorylation by MAPK pathways during HFS-Induced synaptic plasticity in the Rat...

This study examined the role of MAPKs in Tau phosphorylation and synaptic plasticity at perforant pathway-dentate gyrus (PP-DG) synapses following high-frequency stimulation (HFS). In vivo experiments were conducted on adult male Wistar rats under urethane anesthesia. Field potentials (fEPSP and PS) were recorded in the DG granule cell layer in response to PP stimulation. Western blotting assessed total and phosphorylated levels of Tau, ERK1/2, JNK, and P38 MAPK in HFS-induced hippocampus. MAPK inhibition disrupted early somatic potentiation when applied during induction, and JNK inhibition alone impaired late potentiation. Reduced somatic activity correlated with decreased MAPK phosphorylation and Tau phosphorylation at Ser422. Findings suggest that ERK1/2, JNK, and P38 are essential for Tau phosphorylation at Ser422 in HFS-induced hippocampal synapses.