Regulation of synaptic strength by protein phosphatase 1

被引:186
作者
Morishita, W
Connor, JH
Xia, H
Quinlan, EM
Shenolikar, S
Malenka, RC [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, Palo Alto, CA 94304 USA
[2] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
[3] Univ Maryland, Dept Biol Neurobiol & Cognit Sci, College Pk, MD 20742 USA
关键词
D O I
10.1016/S0896-6273(01)00554-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We investigated the role of postsynaptic protein phosphatase 1 (PP1) in regulating synaptic strength by loading CA1 pyramidal cells either with peptides that disrupt PP1 binding to synaptic targeting proteins or with active PP1. The peptides blocked synaptically evoked LTD but had no effect on basal synaptic currents mediated by either AMPA or NMDA receptors. They did, however, cause an increase in synaptic strength following the induction of LTD. Similarly, PP1 had no effect on basal synaptic strength but enhanced LTD. In cultured neurons, synaptic activation of NMDA receptors increased the proportion of PP1 localized to synapses. These results suggest that PP1 does not significantly regulate basal synaptic strength. Appropriate NMDA receptor activation, however, allows PP1 to gain access to synaptic substrates and be recruited to synapses where its activity is necessary for sustaining LTD.
引用
收藏
页码:1133 / 1148
页数:16
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