Specific regulation of immediate early genes by patterned neuronal activity.
Electrical activity shapes development of the nervous system, presumably in part by regulating gene expression. A set of regulatory genes, immediate early genes (IEGs), which are responsive to a number of extrinsic cellular stimuli have been proposed to play a role in coupling such activity to gene expression. Using a semiquantitative polymerase chain reaction assay, we show that in dissociated mouse dorsal root ganglion neurons the expression of two IEGs, c-fos and nur/77, is differentially sensitive to patterns of electrical stimulation. Differences in c-fos activation did not correlate with the peak intracellular calcium [Ca++]i produced by the different stimulation patterns or with residual [Ca++]i following stimulation. However, the net increase in [Ca++]i (calcium time integral) was greater for the pulsed stimulus that activated c-fos (6 impulses/min), compared to the ineffective stimulus (12 impulses/2 min). This system of genes seems suited to mediating the coupling between electrical activity and other functional genes.
Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
H Z
HZ
Sheng
R D
RD
Fields
P G
PG
Nelson
D000200:Action Potentials; D000591:Amino Acid Isomerases / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004558:Electric Stimulation; D005333:Fetus; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D016762:Genes, fos; D007700:Kinetics; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D019696:Peptidylprolyl Isomerase; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D002118:Calcium