SCN-AVP release of mPer1/mPer2 double-mutant mice in vitro

Using an in vitro slice culture setup, SCN-AVP release of cultures made of 10 wildtype and 9 Per1/2 double-mutant mice was assayed. Mice were sacrificed in either the early light phase of the light-dark cycle, or in the early subjective day on the first day of constant dark.Here we report that in arrhythmic homozygous Per1/2 double-mutant mice there is still a diurnal peak in in vitro AVP release from the SCN similar to that of wildtypes but distinctively different from the release pattern from the paraventricular nucleus. Such a modulation of AVP release is unexpected in mice where the circadian clockwork is thought to be disrupted.Our results suggest that the circadian clock in these animals, although deficient in (most) behavioural and molecular rhythms, may still be (partially) functional, possibly as an hourglass mechanism. The level of perturbation of the clock in Per1/2 double mutants may therefore be less than was originally thought.Many behavioural and physiological processes in mammals show circadian (circa 24-hour) rhythms that are entrained to the daily light-dark cycle. These rhythms are governed by internal circadian clocks. The main, light entrainable oscillator is housed in the suprachiasmatic nuclei of the hypothalamus (SCN, [1,2]). As an output of the SCN, Arg8-vasopressin (AVP) is expressed predominantly in the dorsomedial subregion of the SCN, also called the shell [3,4], and circadian rhythms in SCN-AVP transcription, peptide content and release have been reported [5-10].Functionally, SCN-AVP content and release have been correlated with variation in behavioural rhythmicity in voles [8,11,12] but cannot be held exclusively responsible for the control of rhythmic organization of behaviour. Brattleboro rats, not expressing functional AVP, still show circadian rhythms in activity – albeit with a decreased amplitude – and entrain to a light dark schedule [13,14]. Species-specific correlation between strength of circadian organization of behaviour an