Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression

Kimihiko Kameyama, Hey-Kyoung Lee, Mark F. Bear, Richard L Huganir

Research output: Contribution to journalArticle

Abstract

Hippocampal N-methyl-D-aspartate (NMDA) receptor-dependent long-term synaptic depression (LTD) is associated with a persistent dephosphorylation of the GluR1 subunit of AMPA receptors at a site (Ser-845) phosphorylated by cAMP-dependent protein kinase (PKA). In the present study, we show that dephosphorylation of a postsynaptic PKA substrate may be crucial for LTD expression. PKA activators inhibited both AMPA receptor dephosphorylation and LTD. Injection of a cAMP analog into postsynaptic neurons prevented LTD induction and reversed previously established homosynaptic LTD without affecting baseline synaptic transmission. Moreover, infusing a PKA inhibitor into postsynaptic cells produced synaptic depression that occluded homosynaptic LTD. These findings suggest that dephosphorylation of a PKA site on AMPA receptors may be one mechanism for NMDA receptor-dependent homosynaptic LTD expression.

Original languageEnglish (US)
Pages (from-to)1163-1175
Number of pages13
JournalNeuron
Volume21
Issue number5
DOIs
StatePublished - Nov 1998

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Long-Term Synaptic Depression
Cyclic AMP-Dependent Protein Kinases
Protein Kinases
AMPA Receptors
N-Methyl-D-Aspartate Receptors
Protein Kinase Inhibitors
Synaptic Transmission
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression. / Kameyama, Kimihiko; Lee, Hey-Kyoung; Bear, Mark F.; Huganir, Richard L.

In: Neuron, Vol. 21, No. 5, 11.1998, p. 1163-1175.

Research output: Contribution to journalArticle

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