NMDA Receptor Blockade Prevents 
Translation, but Not Transcription, of 
the C -fos Gene Following Stimulation 
With Multiple Extracellular Signals in 
Cultured Cortical Neurons: 
Implications for Plasticity and 
Molecular Memory 
Frank R. Sharp, Klnya Hlsanaga, and Stephen M. Sagar 
INTRODUCTION 
Morgan and Curran (1985) first showed that ionic depolarization of neural crest- 
derived PCI 2 cells induced the c -fos proto-oncogene and that massive brain 
depolarization produced by metrazole-induced seizures induces c -fos in mouse 
brain neurons (Morgan et al. 1987). Although metrazole induced Fos-like 
immunoreactivity (FLI) in cortex, hippocampus, amygdala, and many other 
structures, it did not induce Fos in all brain structures, nor did it induce Fos 
in all neurons in each structure. 
Hunt and colleagues (1987) showed that noxious sensory stimulation induced 
FLI in spinal cord neurons. Dragunow and Robertson (1987) showed that 
kindling induced c -fos in granule cells of the rat dentate gyrus. Sagar and 
colleagues (1988) found that osmotic stimuli induced FLI in hypothalamic 
paraventricular neurons (Sharp et al. 1991), cortical stimulation induced FLI in 
cerebellar Purkinje cell neurons (Sharp et al. 1989a), and seizures induced FLI 
in hippocampus. Sagar and coworkers (1988) suggested that c -fos expression 
could be used to map activated neurons much like the 2- deoxyglucose method 
has been used to map the central nervous system response to physiological 
and pharmacological stimuli. Since then, multiple studies have confirmed 
some of the initial promise of the c -fos “mapping” method (Cole et al. 1 989). 
However, several practical and theoretical problems with F r os have become 
apparent. 
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