changes in hippocampus elicited by seizures are consistent with the activation 
of mechanisms that would tend to counteract the transduction of excitatory 
signals (reviewed in McNamara et al. 1987) (i.e., inhibitory neurotransmission 
is augmented and excitatory neurotransmission is depressed). For example, 
there appears to be an up-regulation of y-aminobutyric acid (GABA) receptors 
and a down-regulation of muscarinic receptors. There is not yet any direct 
evidence to suggest that CIE genes mediate the transcription of these particular 
genes, although appropriate increases in specific CIE genes have been 
observed in the neuronal populations in which these changes occur. However, 
in a second situation there are biochemical data to support the involvement of 
CIE gene products in the regulation of neuropeptide gene expression in 
hippocampus. It is known that proenkephalin transcription is increased in 
the granule cells of the dentate gyrus following seizures (for reviews, see 
McNamara et al. 1987; Morgan and Curran 1991a, 1991b). The timing of 
this induction occurs just after Fos and Jun increase in these same cells 
(Sonnenberg et al. 1989a, 1989b). Furthermore, the proenkephalin promoter 
can be cooperatively transactivated in transient transfection assays by Fos 
and Jun (Sonnenberg et al. 1989b). These data have been interpreted in 
terms of a homeostatic response, whereby recruitment of the CIE genes 
replenishes enkephalin stores that would be depleted by the high levels of 
firing encountered during seizures (i.e., stimulus-transcription coupling is an 
integral component of stimulus-secretion coupling). 
CIE Genes and Neurotrophic Factors 
A third rapid consequence of seizure is the induction, or increased transcription, 
of neurotrophic factors such as nerve growth factor (NGF) and brain-derived 
neurotrophic factor (BDNF). This again appears to occur in the same cells in 
which there is an elevation of CIE gene expression. In addition to the relatively 
rapid responses cited above, seizures and excitatory stimuli also elicit axonal 
sprouting in the CNS (Sutula et al. 1988). This has led to the idea that there is 
a general trophic response to stimulation in brain that has, as one of its early 
components, the induction of CIE genes and growth factors (reviewed in 
Morgan and Curran 1991b). In this model, neurotrophic factors such as BDNF 
may be either CIE genes (as may be the case for NGF) or targets for CIE gene 
products (Gall and Isackson 1989; Hengerer et al. 1990). It is supposed that 
these genes underlie the physical growth response in the nervous system 
following seizure (Sutula et al. 1988; Gall and Isackson 1989; Morgan and 
Curran 1991b). In a wider sense, such an activity-driven growth response in the 
nervous system might be viewed as a general process that provides for long- 
term neuronal plasticity in both normal and neuropathological situations. 
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