DOI: 10.1523/jneurosci.0204-05.2005. AMPA/Kainate Receptor-Mediated Downregulation of GABAergic Synaptic Transmission by Calcineurin after Seizures in the Developing Rat Brain

AMPA/Kainate Receptor-Mediated Downregulation of GABAergic Synaptic Transmission by Calcineurin after Seizures in the Developing Rat Brain

10.1523/jneurosci.0204-05.2005

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Hypoxia is the most common cause of perinatal seizures and can be refractory to conventional anticonvulsant drugs, suggesting an age-specific form of epileptogenesis. A model of hypoxia-induced seizures in immature rats reveals that seizures result in immediate activation of the phosphatase calcineurin (CaN) in area CA1 of hippocampus. After seizures, CA1 pyramidal neurons exhibit a downregulation of GABAAreceptor (GABAAR)-mediated inhibition that was reversed by CaN inhibitors. CaN activation appears to be dependent on seizure-induced activation of Ca2+-permeable AMPA receptors (AMPARs), because the upregulation of CaN activation and GABAAR inhibition were attenuated by GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] or Joro spider toxin. GABAAR β2/3 subunit protein was dephosphorylated at 1 h after seizures, suggesting this subunit as a possible substrate of CaN in this model. Finally,in vivoadministration of the CaN inhibitor FK-506 significantly suppressed hypoxic seizures, and posttreatment with NBQX (2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline) or FK-506 blocked the hypoxic seizure-induced increase in CaN expression. These data suggest that Ca2+-permeable AMPARs and CaN regulate inhibitory synaptic transmission in a novel plasticity pathway that may play a role in epileptogenesis in the immature brain.

Bibliography

Sanchez, R. M., Dai, W., Levada, R. E., Lippman, J. J., & Jensen, F. E. (2005). AMPA/Kainate Receptor-Mediated Downregulation of GABAergic Synaptic Transmission by Calcineurin after Seizures in the Developing Rat Brain. The Journal of Neuroscience, 25(13), 3442â3451.

Authors 5

Russell M. Sanchez (first)
Weimin Dai (additional)
Rachel E. Levada (additional)
Jocelyn J. Lippman (additional)
Frances E. Jensen (additional)

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Dates

Type	When
Created	20 years, 4 months ago (March 30, 2005, 4:03 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 12:38 p.m.)
Indexed	3 weeks, 1 day ago (Aug. 7, 2025, 4:54 a.m.)
Issued	20 years, 4 months ago (March 30, 2005)
Published	20 years, 4 months ago (March 30, 2005)
Published Online	20 years, 4 months ago (March 30, 2005)
Published Print	20 years, 4 months ago (March 30, 2005)

Funders 0

None

BibTeX

@article{Sanchez_2005, title={AMPA/Kainate Receptor-Mediated Downregulation of GABAergic Synaptic Transmission by Calcineurin after Seizures in the Developing Rat Brain}, volume={25}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.0204-05.2005}, DOI={10.1523/jneurosci.0204-05.2005}, number={13}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Sanchez, Russell M. and Dai, Weimin and Levada, Rachel E. and Lippman, Jocelyn J. and Jensen, Frances E.}, year={2005}, month=mar, pages={3442–3451} }

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