Circadian Locomotor Rhythms, but Not Photoperiodic Responses, Survive Surgical Isolation of the SCN in Hamsters

Abstract

Surgical isolation of the suprachiasmatic nuclei (SCN) within a hypothalamic island is reported to produce loss of circadian rhythmicity. The results have been interpreted to indicate that SCN efferents are necessary for the expression of circadian rhythms. It is not clear, however, whether the loss of circadian rhythms in behavioral responses following SCN isolation is attributable to transection of efferents, to loss of cells within the island, or to gliosis produced by the knife cut. To explore this issue, we examined locomotor activity and gonadal state of male golden hamsters housed in constant darkness (DD, with a dim red light for maintenance) for at least 10 weeks following isolation of the SCN from the rest of the brain by cuts by means of a Halasz wire microknife. Brain sections were immunocytochemically stained for the peptides vasoactive intestinal polypeptide (VIP), vasopressin (VP) or neurophysin II (NP II), and neuropeptide Y (NPY) to localize the SCN and to assess its viability, and for glial fibrillary acidic protein (GFAP) to delimit the border of the knife cut. Experimental animals with VIP and VP/NP II immunoreactivity in the SCN within the island retained free-running locomotor rhythms following transection of SCN efferents. Animals with cuts that failed to sever SCN efferents, and sham-operated animals (in which the Halasz knife was lowered but not rotated), also maintained circadian rhythmicity. Hamsters sustaining severe damage to the SCN showed disrupted locomotor activity. In those hamsters that retained circadian locomotor rhythmicity following SCN isolation, gonads failed to regress in DD, demonstrating the absence of an appropriate photoperiodic response. The results suggest a multiplicity of SCN coupling mechanisms in the control of circadian rhythms.

Targeted Microlesions Reveal Novel Organization of the Hamster Suprachiasmatic Nucleus

“…Several points argue against this possibil- ity. First, behavioral rhythms can be supported by a diffusible signal not requiring neural output (Hakim et al, 1991;Silver et al, 1996a;Kramer et al, 2001;Cheng et al, 2002), suggesting that all behavioral rhythms would have been intact if SCN efferents were severed in the present study. In addition, vasopressin neurons in the SCN shell project to both the parasympathetic and sympathetic divisions of the autonomic nervous system in rats (Larsen et al, 1998;Larsen, 1999;Leak et al, 1999;Buijs et al, 2001), suggesting that some projections regulating rhythms in melatonin secretion and heart rate should be intact in animals with small CalB lesions in the present study.…”

The regulation of neuroendocrine function: Timing is everything

“…In contrast to behavioral rhythms (e.g., locomotion, drinking, gnawing), endocrine rhythms require neural projections from the SCN to endocrine targets; endocrine rhythms are abolished after knife cuts severing SCN efferents (Hakim et al, 1991;Nunez and Stephan, 1977) and are not restored in SCN-lesioned transplanted animals (Meyer-Bernstein et al, 1999;Nunez and Stephan, 1977;Silver et al, 1996), presumably due to inadequate neural innervation of the host brain by the graft. Further evidence for a neural SCN output signal regulating hormone secretion is seen in studies of female hamsters.…”

Exploring Spatiotemporal Organization of SCN Circuits

“…The SCN produces both synaptic and diffusible output signals (Hakim et al 1991;Silver et al 1996). Neural efferents appear to be necessary for SCN control of neuroendocrine responses but not for activity-dependent rhythms such as drinking, gnawing, and temperature regulation (Lehman et al 1987;Hakim et al 1991;Meyer-Bernstein et al 1999). Finally, individual SCN neurons display circadian rhythmicity upon dispersion (Welsh et al 1995).…”

“…Furthermore, fetal SCN grafts can restore behavioral rhythms in SCN-lesioned animals (Lehman et al 1987;Ralph et al 1990). The SCN produces both synaptic and diffusible output signals (Hakim et al 1991;Silver et al 1996). Neural efferents appear to be necessary for SCN control of neuroendocrine responses but not for activity-dependent rhythms such as drinking, gnawing, and temperature regulation (Lehman et al 1987;Hakim et al 1991;Meyer-Bernstein et al 1999).…”