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 | |
| State | Published - Nov 1998 |
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ASJC Scopus subject areas
- Neuroscience(all)
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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 journal › Article
}
TY - JOUR
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
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.
UR - http://www.scopus.com/inward/record.url?scp=0032215153&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032215153&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(00)80633-9
DO - 10.1016/S0896-6273(00)80633-9
M3 - Article
C2 - 9856471
AN - SCOPUS:0032215153
VL - 21
SP - 1163
EP - 1175
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 5
ER -