Neuronal Hyperactivity Induces Tau Phosphorylation Selectively in Excitatory Pyramidal Neurons Which Contributes to GluA2 Regulation

Chronic bicuculline-induced hyperactivity in rat hippocampal neurons selectively increases dendritic tau phosphorylation at S202/T205 in excitatory CA1 and CA3 pyramidal neurons.

• Why it matters: The molecular link between tau regulation and neuronal hyperexcitability—dysregulated in Alzheimer’s disease—remains unclear, especially how endogenous tau responds to activity.
• What they did: Rat hippocampal neurons were treated with bicuculline or tetrodotoxin for 24 hours; phospho-tau at S202/T205 was measured, correlated with cfos after bicuculline, and blocked by PKA inhibition.
• The result: Wild-type tau overexpression increased S202/T205 phosphorylation and reduced surface GluA2, prevented by phospho-site mutation; in mice, chronic low-dose picrotoxin increased endogenous S202/T205 phosphorylation in CA3 and CA1 linked to cfos.