Peripheral clocks

Sassone-Corsi We know that the transplanted SCN doesn t receive normal input from the retina. Is it possible that the transplanted SCN is not communicating with the rest of peripheral tissues in the same way I am not sure that the experiment of Bert van der Horst will teU us whether the transplanted SCN is able to entrain a non-functioning peripheral clock. 

However, there is an apparently important difference between SCN and non-SCN rhythms in vitro-. SCN explants remain rhythmic while other regions of the brain and peripheral tissues damp after a minimum of two, but a maximum of about 15 cycles (Fig. 1). The robustness and persistence of the rhythmicity depends on the tissue and does vary in individual cultures. It has been assumed from results like these that the SCN is a self-sustained pacemaker while peripheral clocks are damped oscillators, but it cannot be excluded that in isolated peripheral tissues, I erl may damp despite the persistent rhythmicity of other clock components or that the cultures lack some factor continuously present in vivo that is required for sustained rhythmicity of non-SCN tissue. 

Use of the Per-luc rat model made possible studies on the role of food in the entrainment of these and other peripheral clocks (Stokkan et al 2001). Rats were fed under restriction during the day. Organ explants from these rats were then cultured and the phases of the Per-luc rhythm were shifted by 12 hours in the liver (Fig. 3), and somewhat lesser amounts in stomach and colon (Fig. 4B). The SCN was completely unaffected by the feeding schedule. 

Food may also result in diffusible signals affecting the phase of peripheral clocks. For example, when feeding of nocturnal animals like mice is restricted to daytime... 

Pando MP, Morse D, Cermakian N, Sassone-Corsi P 2002 Phenotypic rescue of a peripheral clock genetic defect via SCN hierarchical dominance. Cell 110 107—117 Plautz JD, Kaneko M, Hall JC, Kay SA 1997 Independent photoreceptive circadian clocks throughout Drosophila. Science 278 1632-1635... 

Sassone-Corsi That s a good question, and we haven t done this. I would expect the effects to be from the SCN, but we need to do this experiment. I would love to see a SCN transplant in a Clock mutant mouse. But if what Bert van der Horst said in his paper (Bonnefont et al 2003, this volume) is true, that peripheral clocks are not working in Cry double knockouts where a normal SCN is introduced, this teUs me that all peripheral oscillators are not crucial for motor rhythmic activity. Could the SCN be the only thing responsible for aU the rhythmic activity I am not sure how much peripheral tissues are working in those Cry double knockouts. 

Sehgal My question was, if you see a short period in culture, what difference does this make to the peripheral clock invivo7... 

FIG. 4. Diagram of a circadian system in mammals. The master clock in the SCN entrains all non-SCN clocks in the brain and peripheral organs. Light information enters into the SCN, and non-photic information such as restriction feeding and maternal care enter into the peripheral clocks. Additionally, this scheme proposes the existence of non-photic entrainment from information from non-SCN clocks. 

Young Do excitable membranes exist in the liver How does this relate to peripheral clocks ... 

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