DOI: 10.1523/jneurosci.20-10-03529.2000. Developmentally Regulated NMDA Receptor-Dependent Dephosphorylation of cAMP Response Element-Binding Protein (CREB) in Hippocampal Neurons

Developmentally Regulated NMDA Receptor-Dependent Dephosphorylation of cAMP Response Element-Binding Protein (CREB) in Hippocampal Neurons

10.1523/jneurosci.20-10-03529.2000

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Developmental changes in the signaling properties of NMDA receptors have been proposed to underlie the loss of plasticity that accompanies brain maturation. Calcium influx through postsynaptic NMDA receptors can stimulate neuronal gene expression via signaling pathways such as the Ras-MAP kinase (MAPK) pathway and the transcription factor cAMP response element-binding protein (CREB). We analyzed MAPK (Erk1/2) and CREB activation in response to NMDA receptor stimulation during the development of hippocampal neurons in culture. At all stages of development NMDA stimulation induced a rapid phosphorylation of CREB on Ser-133 (phospho-CREB). However, the time course of decline in phospho-CREB changed dramatically with neuronal maturation. At 7 din vitro(7 DIV) phospho-CREB remained elevated 2 hr after strong NMDA stimulation, whereas at 14 DIV phospho-CREB rose only transiently and fell back to below basal levels within 30 min. Moreover, at 14 DIV, but not at 7 DIV, NMDA receptor stimulation induced a dephosphorylation of CREB that previously had been phosphorylated by KCl depolarization or forskolin, suggesting an NMDA receptor-dependent activation of a CREB phosphatase. There was no developmental change in the time course of phospho-CREB induction that followed KCl depolarization or PKA activation, nor was there a developmental change in the time course of phospho-Erk1/2 induced by NMDA receptor activation. We suggest that, during neuronal maturation, NMDA receptor activation becomes linked specifically to protein phosphatases that act on Ser-133 of CREB. Such a developmentally regulated switch in the mode of NMDA receptor coupling to intracellular signaling pathways may contribute to the changes in neural plasticity observed during brain development.

Bibliography

Sala, C., Rudolph-Correia, S., & Sheng, M. (2000). Developmentally Regulated NMDA Receptor-Dependent Dephosphorylation of cAMP Response Element-Binding Protein (CREB) in Hippocampal Neurons. The Journal of Neuroscience, 20(10), 3529â3536.

Authors 3

Carlo Sala (first)
Sheila Rudolph-Correia (additional)
Morgan Sheng (additional)

References 43 Referenced 157

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Dates

Type	When
Created	7 years, 4 months ago (April 6, 2018, 2 p.m.)
Deposited	1 month, 3 weeks ago (July 3, 2025, 9:47 a.m.)
Indexed	1 month, 3 weeks ago (July 4, 2025, 12:07 a.m.)
Issued	25 years, 3 months ago (May 15, 2000)
Published	25 years, 3 months ago (May 15, 2000)
Published Online	25 years, 3 months ago (May 15, 2000)
Published Print	25 years, 3 months ago (May 15, 2000)

Funders 0

None

BibTeX

@article{Sala_2000, title={Developmentally Regulated NMDA Receptor-Dependent Dephosphorylation of cAMP Response Element-Binding Protein (CREB) in Hippocampal Neurons}, volume={20}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.20-10-03529.2000}, DOI={10.1523/jneurosci.20-10-03529.2000}, number={10}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Sala, Carlo and Rudolph-Correia, Sheila and Sheng, Morgan}, year={2000}, month=may, pages={3529–3536} }

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