In Vivo Monitoring of Multi-Unit Neural Activity in the Suprachiasmatic Nucleus Reveals Robust Circadian Rhythms in Period1(−/−) Mice

The master pacemaker in the suprachiasmatic nucleus (SCN) controls daily rhythms of behavior in mammals. C57BL/6J mice lacking Period1 (Per1(−/−)) are an anomaly because their SCN molecular rhythm is weak or absent in vitro even though their locomotor activity rhythm is robust. To resolve the contradiction between the in vitro and in vivo circadian phenotypes of Per1(−/−) mice, we measured the multi-unit activity (MUA) rhythm of the SCN neuronal population in freely-behaving mice. We found that in vivo Per1(−/−) SCN have high-amplitude MUA rhythms, demonstrating that the ensemble of neurons is driving robust locomotor activity in Per1(−/−) mice. Since the Per1(−/−) SCN electrical activity rhythm is indistinguishable from wild-types, in vivo physiological factors or coupling of the SCN to a known or unidentified circadian clock(s) may compensate for weak endogenous molecular rhythms in Per1(−/−) SCN. Consistent with the behavioral light responsiveness of Per1 (−/−) mice, in vivo MUA rhythms in Per1 (−/−) SCN exhibited large phase shifts in response to light. Since the acute response of the MUA rhythm to light in Per1(−/−) SCN is equivalent to wild-types, an unknown mechanism mediates enhanced light responsiveness of Per1(−/−) mice. Thus, Per1(−/−) mice are a unique model for investigating the component(s) of the in vivo environment that confers robust rhythmicity to the SCN as well as a novel mechanism of enhanced light responsiveness.