Cell-type-specific H₂O₂ elevation reveals distinct redox sensitivity оf hippocampal rhythmic activity

Redox signaling regulates neuronal function, yet how acute cell-specific hydrogen peroxide (H₂O₂) elevation affects hippocampal network oscillations remains unclear. Using a chemogenetic approach in mouse hippocampal slices and in vivo, we induced controlled intracellular H₂O₂ production selectively in pyramidal cells or interneurons and examined the effects on sharp-wave ripples (SPW-Rs) and gamma oscillations. Pyramidal-cell H₂O₂ reduced SPW-R amplitude, propagation success, and CA3-CA1 synchrony, accompanied by a reversible 25% reduction in EPSC amplitude without affecting IPSCs or paired-pulse ratios, indicating a postsynaptic mechanism. Interneuron-specific H₂O₂ reduced SPW-R frequency and propagation success without altering propagation velocity. In striking contrast, gamma oscillations, whether evoked optogenetically in slices or recorded spontaneously in vivo, were resistant to H₂O₂ elevation regardless of cell type targeted. These findings reveal that SPW-Rs and gamma oscillations exhibit differential sensitivity to acute H₂O₂, with cell-type-specific effects on ripples but universal resistance of gamma activity. Because the two rhythms support distinct cognitive operations, this dissociation suggests that transient redox signals may selectively constrain memory consolidation while leaving active encoding-related processing intact, and that the cellular source of H₂O₂ determines which network state is affected.