Developmental switch in requirement for PKA RIIβ in NMDA-receptor-dependent synaptic plasticity at Schaffer collateral to CA1 pyramidal cell synapses

NEUROPHARMACOLOGY

卷:56

Article

Yang, Yupeng¹  Takeuchi, Koichi¹  Rodenas-Ruano, Alma¹  Takayasu, Yukihiro¹  Bennett, Michael V. L.¹  Zukin, R. Suzanne¹ 

[1] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA

关键词: PKA;    PKA type II regulatory subunit;    PKA RII beta knockout mice;    NMDA receptors;    Synaptic plasticity;    Long-term potentiation;    Long-term depression;    Hippocampus;    CA1 synapses;   

DOI  :  10.1016/j.neuropharm.2008.08.013

来源: Elsevier

【 摘 要 】

The cAMP/protein kinase A (PKA) signaling cascade is crucial for synaptic plasticity in a wide variety of species. PKA regulates Ca2+ permeation through NMDA receptors (NMDARs) and induction of NMDAR-dependent synaptic plasticity at the Schaffer collateral to CA1 pyramidal cell synapse. Whereas the role of PKA in induction of NMDAR-dependent LTP at CA1 synapses is established, the identity of PKA isoforms involved in this phenomenon is less clear. Here we report that protein synthesis-independent NMDAR-dependent LTP at the Schaffer collateral-CA1 synapse in the hippocampus is deficient, but NMDAR-dependent LTD is normal, in young (postnatal day 10 (P10)-P14) mice lacking PKA RII beta, the PKA regulatory protein that links PKA to NMDARs at synaptic sites. In contrast, in young adult (P21-P28) mice lacking PKA RII beta, LTP is normal and LTD is abolished. These findings indicate that distinct PKA isoforms may subserve distinct forms of synaptic plasticity and are consistent with a developmental switch in the signaling cascades required for LTP induction. (C) 2008 Elsevier Ltd. All rights reserved.

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