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

doi:10.1016/S0896-6273(00)80633-9

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	1163-1175
Number of pages	13
Journal	Neuron
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/S0896-6273(00)80633-9
State	Published - Nov 1998

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/S0896-6273(00)80633-9

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@article{f74f177a057042b6b3182a7076902558,

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

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.",

author = "Kimihiko Kameyama and Lee, {Hey Kyoung} and Bear, {Mark F.} and Huganir, {Richard L.}",

note = "Funding Information: We thank Elizabeth Quinlan, Kimberly Huber, Benjamin Philpot, David Brautigan, and Sherish Shenolikar for helpful discussions. This work was partly supported by a grant from the Charles A. Dana Foundation. Dr. Kameyama was supported by the Human Frontiers Science Program.",

year = "1998",

month = nov,

doi = "10.1016/S0896-6273(00)80633-9",

language = "English (US)",

volume = "21",

pages = "1163--1175",

journal = "Neuron",

issn = "0896-6273",

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T1 - Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression

AU - Kameyama, Kimihiko

AU - Lee, Hey Kyoung

AU - Bear, Mark F.

AU - Huganir, Richard L.

N1 - Funding Information: We thank Elizabeth Quinlan, Kimberly Huber, Benjamin Philpot, David Brautigan, and Sherish Shenolikar for helpful discussions. This work was partly supported by a grant from the Charles A. Dana Foundation. Dr. Kameyama was supported by the Human Frontiers Science Program.

PY - 1998/11

Y1 - 1998/11

N2 - 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.

AB - 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.

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JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 5

ER -

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

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