Control of programmed cell death by distinct electrical activity patterns.
Electrical activity and sufficient supply with survival factors play a major role in the control of apoptosis in the developing cortex. Coherent high-frequency neuronal activity, which efficiently releases neurotrophins, is essential for the survival of immature neurons. We studied the influence of neuronal activity on apoptosis in the developing cortex. Dissociated cultures of the newborn mouse cerebral cortex were grown on multielectrode arrays to determine the activity patterns that promote neuronal survival. Cultures were transfected with a plasmid coding for a caspase-3-sensitive fluorescent protein allowing real-time analysis of caspase-3-dependent apoptosis in individual neurons. Elevated extracellular potassium concentrations (5 and 8 mM), application of 4-aminopyridine or the γ-aminobutyric acid-A receptor antagonist Gabazine induced a shift in the frequency distribution of activity toward high-frequency bursts. Under these conditions, a reduction or delay in caspase-3 activation and an overall increase in neuronal survival could be observed. This effect was dependent on the activity of phosphatidylinositol-3 kinase, as blockade of this enzyme abolished the survival-promoting effect of high extracellular potassium concentrations. Our data indicate that increased network activity can prevent apoptosis in developing cortical neurons.
Institute of Physiology and Pathophysiology, University Medical Center, Johannes Gutenberg University, D-55128 Mainz, Germany.
Antje
A
Golbs
Birgit
B
Nimmervoll
Jyh-Jang
JJ
Sun
Irina E
IE
Sava
Heiko J
HJ
Luhmann
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D011724:Pyridazines; C049853:gabazine