The Suprachiasmatic Nucleus and the Circadian Timing System - Progress in Molecular Biology and Translational Science - page 8

circadian function. I had extensive experience making localized stereotactic
lesions in the rat brain but did not have the animal facilities to study rest-
activity rhythms. However, I was performing biochemical assays in my lab-
oratory and decided to analyze the effects of SCN ablation on the adrenal
corticosterone rhythm in the rat. This is a robust rhythm and the only dis-
advantage was that we could show only group effects as animals had to be
sacrificed at four time periods around the clock. Control groups included a
blinded group, a group with electrolytic lesions of the SCN, a group with a
Halasz knife 51 coronal transection of the medial hypothalamus rostral to the
SCN, one with a transection just caudal to the optic chiasm and a sham-
operated group. The blinded group showed a shift in the peak of the rhythm
compared to controls indicating a free running rhythm. The SCN lesion
group and the group with knife cuts just caudal to the SCN showed a loss
of the adrenal rhythm whereas the group with knife cuts rostral to the SCN
had no rhythm impairment. Thus, these data are consistent with the view
that the SCN is a circadian pacemaker. SCN lesions abolish the rhythm,
and a knife cut rostral to the SCN does not affect rhythmicity indicating that
SCN lesions do not alter rhythm generation by transecting pathways run-
ning near or through the SCN. That knife cuts caudal to the SCN also abol-
ish the rhythm indicating that SCN projections caudal to the nucleus are
crucial to rhythm control ( Ref. 52 ; Fig. 1.2 ). Loss of the rest-activity rhythm
after SCN lesions was reported in the same year. 53 Over the next 20 years,
the effects of SCN ablation were studied many times (cf. Refs. 54-56 , for
detailed reviews). With some exceptions that will be discussed later, SCN
lesions reliably abolished behavioral and physiological rhythms. Three other
sets of data were extremely important. First, Schwartz and colleagues reported
an in vivo rhythm in glucose utilization employing a new method. 57-59 Sec-
ond, Inouye and Kawamura 60 demonstrated circadian rhythms in multiunit
firing rate recorded in vivo from the SCN in the intact brain and in a hypo-
thalamic island isolated from the remaining brain. In the latter case, rhythms in
other brain areas were lost indicating that the SCN was the source of rhyth-
micity. 61 Subsequently, three groups reported single-unit rhythms in the SCN
in hypothalamic slices in vitro . 62-64 No other area sampled showed neuronal
rhythms, and the peak of the firing rate rhythms was in the middle of what
would have been subjective day in the intact animal, and the peak of the
rhythm in glucose utilization. 58 Second, transplants containing fetal SCN
placed in the third ventricle of arrhythmic hosts with SCN lesions restored
locomotor activity rhythms (Refs. 65-67 , 136 ) . A crucial study demonstrated
that the transplant, not the host, determined the period of the restored