Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors

Luchkina, N.V., Huupponen, J., Clarke, V.R., Coleman, S.K., Keinänen, K., Taira, T. and Lauri, S.E. 2014. Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors. Proceedings of the National Academy of Sciences of the United States of America. 111 (11), p. 4321–4326. doi:10.1073/pnas.1315769111

TitleDevelopmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors
AuthorsLuchkina, N.V., Huupponen, J., Clarke, V.R., Coleman, S.K., Keinänen, K., Taira, T. and Lauri, S.E.
Abstract

The AMPA-receptor subunit GluA4 is expressed transiently in CA1 pyramidal neurons at the time synaptic connectivity is forming, but its physiological significance is unknown. Here we show that GluA4 expression is sufficient to alter the signaling requirements of long-term potentiation (LTP) and can fully explain the switch in the LTP kinase dependency from PKA to Ca2(+)/calmodulin-dependent protein kinase II during synapse maturation. At immature synapses, activation of PKA leads to a robust potentiation of AMPA-receptor function via the mobilization of GluA4. Analysis of GluA4-deficient mice indicates that this mechanism is critical for neonatal PKA-dependent LTP. Furthermore, lentiviral expression of GluA4 in CA1 neurons conferred a PKA-dependent synaptic potentiation and LTP regardless of the developmental stage. Thus, GluA4 defines the signaling requirements for LTP and silent synapse activation during a critical period of synapse development.

Keywordsglutamate receptor; hippocampus; synaptic transmission
JournalProceedings of the National Academy of Sciences of the United States of America
Journal citation111 (11), p. 4321–4326
ISSN1091-6490
Year2014
PublisherNational Academy of Sciences of the United States of America
Digital Object Identifier (DOI)doi:10.1073/pnas.1315769111
Publication dates
Published18 Mar 2014

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