Immediate Early Genes: Their 
Involvement in Physiological and 
Pathological Responses in the 
Nervous System 
Michael D. Hayward Tom Curran , and James /. Morgan 
INTRODUCTION 
The Cellular Immediate Early Gene Response 
The application of an extracellular stimulus to a cell has two types of general 
conseqences: a rapid, usually short-lived, response that is protein synthesis 
independent and a more persistent action that frequently requires gene 
transcription. The latter finding led to a search for the signaling molecules that 
couple a stimulus to the transcriptional machinery of the cell. A quantum leap 
in understanding this problem came with the discovery that several proto- 
oncogenes, including c-/bs, c-jun , and c -myc, are rapidly (within minutes) 
induced by a diverse array of extracellular stimuli. Since these genes encode 
nuclear proteins, it was supposed that they might be involved in stimulus- 
dependent regulation of transcription (Curran and Morgan 1987; Lau and 
Nathans 1987). Subsequent studies have confirmed and expanded this basic 
notion. 
Cellular Immediate Early Genes and Learning 
For the neurobiologist, alterations in gene expression have long been 
supposed to underlie several key aspects of neurophysiology and, indeed, 
neuropathology. For example, there are many studies dating back to the early 
1960s indicating that protein synthesis is essential for memory acquisition in 
both vertebrates and invertebrates (for reviews, see Barondes 1965, 1970, 
1975; Agranoff 1972; Goelet et al. 1986). Indeed, based on the prevailing 
literature of the time, Barondes (1975) suggested that memory acquisition was 
composed of two processes. The first process began immediately upon training 
(i.e., it had no measurable lag), lasted for hours, and involved posttranslational 
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