Kameyama K, Lee H K, Bear M F, Huganir R L
Howard Hughes Medical Institute, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Neuron. 1998 Nov;21(5):1163-75. doi: 10.1016/s0896-6273(00)80633-9.
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.
海马体中依赖N-甲基-D-天冬氨酸（NMDA）受体的长期突触抑制（LTD）与α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体GluR1亚基在一个由环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）磷酸化的位点（丝氨酸845）的持续去磷酸化有关。在本研究中，我们表明突触后PKA底物的去磷酸化可能对LTD的表达至关重要。PKA激活剂抑制了AMPA受体的去磷酸化和LTD。将cAMP类似物注入突触后神经元可阻止LTD的诱导，并逆转先前建立的同突触LTD，而不影响基线突触传递。此外，将PKA抑制剂注入突触后细胞会产生突触抑制，从而阻断同突触LTD。这些发现表明，AMPA受体上PKA位点的去磷酸化可能是NMDA受体依赖性同突触LTD表达的一种机制。
