An NMDA receptor/nitric oxide cascade in presynaptic parallel fiber-Purkinje neuron long-term potentiation.
Plasticity of synaptic transmission between parallel fiber (PF) and Purkinje neurons (PNs) is widely accepted as a cellular model for certain forms of cerebellar learning. Whereas the signaling cascades involved in postsynaptically expressed bidirectional long-term changes at PF-PN synapses are well investigated, data on presynaptically expressed long-term potentiation (LTP) are incomplete and controversial. Here we used transgenic mice that express a fluorescent protein Ca2+ sensor in PFs to demonstrate LTP of PF presynaptic Ca2+ transients after PF stimulation with 120 pulses at 4 Hz. Potentiation of the presynaptic Ca2+ transients correlated with the expression of simultaneously recorded LTP of PF-PN synaptic transmission and was suppressed by a protein kinase A inhibitor. Moreover, this presynaptically expressed form of LTP clearly required activation of an NMDA receptor/nitric oxide pathway, in contrast with the majority of previous reports. Blockade of NMDA receptors did not affect the PF Ca2+ transients induced during 4 Hz stimulation, indicating that the NMDA receptors required for the induction of presynaptic PF LTP are not localized in PFs.
Qiu
De-lai
DL
Laboratory for Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
Knöpfel
Thomas
T
D000818:Animals; D001711:Biotransformation; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D002118:Calcium