Loss of PEA-15 Alters ERK/MAPK Signaling and Circadian Function in the Suprachiasmatic Nucleus

Loss of PEA-15 in mice significantly reduces clock-gated and light-evoked ERK activation in the suprachiasmatic nucleus, linking PEA-15 to ERK/MAPK signaling.

• Why it matters: ERK/MAPK signaling and photic entrainment are key to circadian timing, yet how PEA-15 regulates SCN clock function and light responsiveness was unclear.
• What they did: Using PEA-15 knockout (PEA-15-/-) mice, the study measured ERK activation in SCN neurons and tested circadian timing, free-running period, locomotor activity, and light resetting with jet-lag and Aschoff type I paradigms.
• The result: In constant darkness, PEA-15-/- mice showed a significantly shorter free-running period and reduced locomotor activity, with blunted phase-delay and accelerated entrainment to phase-advancing light.