Postsynaptic calcineurin activity downregulates synaptic transmission by weakening intracellular Ca2+ signaling mechanisms in hippocampal CA1 neurons.
Protein phosphorylation and dephosphorylation are believed to functionally couple neuronal activity and synaptic plasticity. Our previous results indicated that postsynaptic Ca2+/calmodulin (CaM) signaling pathways play an important role in setting synaptic strength, and calcineurin (CaN) activity limits synaptic responses during basal synaptic transmission and long-term potentiation expression. The inhibition of postsynaptic CaN activity by FK-506 or an autoinhibitory peptide induced synaptic potentiation in hippocampal slices, which occludes tetanus-induced LTP. FK-506-induced synaptic potentiation was expressed in adult but not young rats. To elucidate mechanisms underlying CaN-inhibited synaptic potentiation, we co-injected certain agents affecting Ca2+ signaling pathways with CaN inhibitors into CA1 neurons. Synaptic potentiation induced by FK-506 was significantly attenuated by co-injecting BAPTA, heparin/dantrolene (inhibitors of intracellular Ca2+ release), a CaM-binding peptide, or CaM-KII/PKC pseudosubstrate peptides. These results indicate that postsynaptic CaN activity can downregulate evoked synaptic transmission by weakening intracellular Ca2+ signals and downstream protein kinase activities.
Wang
J H
JH
Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, Texas 77225, USA.
Kelly
P T
PT
D000375:Aging / Q000502:physiology; D000818:Animals; D019703:Calcineurin; D002118:Calcium / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011493:Protein Kinase C; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology
D002148:Calmodulin-Binding Proteins; D010446:Peptide Fragments; D004533:Egtazic Acid; D006493:Heparin; D011493:Protein Kinase C; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D003620:Dantrolene; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D016559:Tacrolimus