Developmental switch in requirement for PKA RIIbeta in NMDA-receptor-dependent synaptic plasticity at Schaffer collateral to CA1 pyramidal cell synapses.
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 RIIbeta, the PKA regulatory protein that links PKA to NMDARs at synaptic sites. In contrast, in young adult (P21-P28) mice lacking PKA RIIbeta, 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.
Yang
Yupeng
Y
Dominick P. Purpura Department of Neuroscience, Kennedy Center Room 602B, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Takeuchi
Koichi
K
Rodenas-Ruano
Alma
A
Takayasu
Yukihiro
Y
Bennett
Michael V L
MV
Zukin
R Suzanne
RS
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / Q000172:deficiency / Q000502:physiology*; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine
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