IEGs, members of various families, all interacting with one another and with 
other second and third messengers to affect several transcriptional regulating 
sites and, thus, altering gene expression. What has become clear is that 
these genes probably play a role in postmitotic tissue, the best example 
being neurons in the brain. However, it should be kept in mind that some 
IEGs may perform not as messengers in tightly linked signaling systems but 
as “housekeeping” genes, regulating the response of cellular metabolism to 
particular alterations in conditions. For example, it is remarkable to note the 
similarity between the activation of c-fos in cerebral cortex ipsilateral to a 
lesion (Dragunow and Robertson 1988; Herrera and Robertson 1989, 1990a) 
and the activation of the heat shock protein, HSP-71 (Gonzalez et al. 1 989). 
However, having raised this caution, it is clear from several examples in the 
brain that there is good circumstantial evidence that c -fos and other IEGs 
play an important role in the transduction of neuronal stimulation into specific 
neuronal changes (plasticity); this neuronal stimulation can be elicited by 
physiological (e.g., light, pain) or pharmacological means. 
IEG ACTIVATION: A MAPPING TOOL FOR THE BRAIN? 
It has been apparent since the work of Hunt and colleagues (1987) on the 
effects of pain on the induction of c -fos in spinal cord that, apart from the 
importance that the IEGs might play in cellular function in brain systems, the 
robust response of the IEGs might be generally useful as an indication of 
transsynaptic activation and in the mapping of polysynaptic pathways in the 
brain. This usefulness has generally been confirmed in many subsequent 
studies (e.g., Sagar et al. 1988; Rusak et al. 1990, in press; MacDonald et 
al. 1990). This does not detract from the significance of IEGs as possibly 
extremely important “third or fourth messengers” in signal transduction. 
However, it does add an extremely important dimension to the uses of IEG 
activation. 
EXPRESSION OF IEGs IN THE MAMMALIAN BRAIN: KINDLING, 
LONG-TERM POTENTIATION, AND SEIZURES 
Induction of IEGs has now been demonstrated in several systems in the brain 
and in association with several neurotransmitter systems. The initial studies 
that suggested an important role for IEGs in the brain described activation of 
c -fos and other IEGs in the brain following drug-induced seizure activity 
(Morgan et al. 1987; Dragunow and Robertson 1987a; Saffen et al. 1988; 
Le Gal La Salle 1988; Sonnenberg et al. 1989). A single electrical stimulus 
to amygdala or hippocampus (at an intensity known to lead to the longlasting 
effect known as kindling) will also produce an increase in c-Fos protein in the 
hippocampal formation, with an especially high concentration in the dentate 
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