Endogenous protein kinase A inhibitor (PKIalpha) modulates synaptic activity.
Protein kinase A (PKA) has long been known to be involved in major regulatory mechanisms underlying synaptic plasticity and complex behaviors such as learning and memory. The endogenous PKA inhibitor, PKIalpha, has been extensively studied for its effects on PKA and PKA-mediated signal transduction. Clear functions for PKIalpha in vivo, however, remain to be established. Here we describe that several forms of synaptic stimulation in the rat hippocampus cause a dramatic decrease in the concentration of PKIalpha in dentate granule cells. Furthermore, chronic infusion of antisense oligonucleotides against PKIalpha into the rat brain results in a dramatic reduction of the excitability of these neurons and elimination of their ability to exhibit long-term potentiation (LTP) and long-term depression (LTD), suggesting a stimulus-dependent regulatory role for PKIalpha in PKA signal transduction.
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
L
L
de Lecea
J R
JR
Criado
S
S
Rivera
W
W
Wen
E
E
Soriano
S J
SJ
Henriksen
S S
SS
Taylor
C M
CM
Gall
J G
JG
Sutcliffe
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016375:Antisense Elements (Genetics); D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology / Q000648:ultrastructure; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D017774:Long-Term Potentiation / Q000502:physiology; D008854:Microscopy, Electron; D019599:Mossy Fibers, Hippocampal / Q000201:enzymology / Q000648:ultrastructure; D009474:Neurons / Q000201:enzymology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000201:enzymology*; D009435:Synaptic Transmission / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D016375:Antisense Elements (Genetics); D002352:Carrier Proteins; D004791:Enzyme Inhibitors; C491525:Pkia protein, rat; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases