Regulation of the Phase and Period of Circadian Rhythms Restored by Suprachiasmatic Transplants

Abstract

The influence of exogenous signals on circadian rhythms restored by transplants of the suprachiasmatic nucleus (SCN) of the hypothalamus has received little study The authors tested the responsiveness of hamsters bearing SCN transplants to photic and pharmacological treatments. Light intensities as high as 6500 lux were insufficient to produce entrainment, although masking was observed frequently. Triazolam failed to produce statistically significant phase shifts when administered during the subjective day, but 2 animals bearing functional SCN grafts responded to this benzodiazapine during the subjective night. The authors next tested the hypothesis that the host can retain circadian aftereffects that influence the period of the circadian system reconstituted by the graft. Intact hamsters were entrained to light:dark cycles of short (23.25-h) and long (25-h) periods (T) for at least 3 months. Control hamsters released into constant darkness exhibited profound and long-lasting aftereffects of entrainment to T cycles. Hamsters that received SCN lesions after exposure to these T cycles and SCN grafts 3 weeks later exhibited marginal but statistically significant aftereffects that disappeared within 3 months. On subsequent transfer to constant light, τ lengthened by 0.25 ± .06 h in hamsters with intact SCN (p < .05). Animals bearing SCN grafts continued to free run in constant light but differed from intact animals in that circadian period did not lengthen. Functional SCN grafts contained vasoactive intestinal polypeptide (VIP), neurophysin (NP), and cholecystokinin (CCK) immunoreactive (ir) cells. Inputs of neuropeptide Y- and serotonin-ir fibers from the host brain to grafted SCN peptide cell clusters were variable. Limited observations using retrograde and anterograde tracers do not support the existence of extensive input to the graft. Retinal input overlapped only rarely with clusters of VIP-ir, CCK-ir, or NP-ir cells. The authors conclude