lEGs AND CONTROL OF CIRCADIAN RHYTHMS 
In mammals, the suprachiasmatic nucleus (SCN) is the site of the central 
control mechanism for the regulation of circadian rhythms (Rusak and 
Zucker 1979). The “clock” in the SCN is “set” (entrained to the environmental 
lighting) by neurons in the retina that project to the SCN. Exposing an animal 
to light during its “dark” phase will alter or shift the circadian rhythm. Exposing 
rats or hamsters to light during the night will result in the induction of c -fos 
and NGFI-A (Rusak et al. 1990) and other lEGs (Rusak et al., in press). 
Most important, light will induce c -fos only during the “expected” dark phase 
in animals kept in total darkness. Such animals continue to maintain the 
circadian rhythm established before they were placed in total darkness. 
During the “expected” light phase, exposure to light will not lead to the 
induction of c -fos and other lEGs (Rusak et al. 1990, in press). There is 
also a good correlation between the intensity of the light required to produce 
the physiological effect (a shift in the circadian rhythm) and the induction 
of mRNA production (Kornhauser et al. 1990). There is some evidence that 
the photic induction of lEGs in the SCN is regulated by glutamate receptors 
of the NMDA type, at least in part (Abe et al. 1991). The mechanism that 
prevents light stimulation from inducing the lEGs during the subjective day is 
pretranscriptional but otherwise unknown. Feasible mechanisms include the 
possibilities that the retinal ganglion cells do not transmit the information or 
that the receptors in the SCN exhibit rhythmic sensitivity. It appears that the 
NMDA type of glutamate receptor is at least involved, but another possibility 
is that the sensitivity of the NMDA receptor is being regulated via alterations 
in the depolarization state of the SCN neurons by another endogenous or 
exogenous factor. 
DAMAGE-INDUCED ACTIVATION OF lEGs 
Damage to tissues often produces homeostatic responses that include the 
release of growth factor and induction of cell proliferation. Therefore, it is 
not surprising that such brain damage will produce widespread activation of 
c -fos (Dragunow and Robertson 1988). Indeed, early experiments attempting 
to look at the activation of IEG synthesis in slices had been compromised by 
the fact that the process of preparing the slice produced a maximum activation 
of IEG expression (S.P. Hunt, personal communication, November 1987). 
Similarly, when first reported, damage-induced activation of lEGs in brain in 
vivo was (and is) a serious complication for in vivo experimentation. It meant 
that introduction of a cannula or an electrode into brain, by itself, produced 
significant IEG expression. Furthermore, induction of lEGs was seen not only 
adjacent to the site of damage but also in parts of the cortex remote to the 
damage (Dragunow and Robertson 1988; Herrera and Robertson 1989, 1990a, 
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