A different form of long-lasting potentiation revealed in tissue plasminogen activator mutant mice.
The establishment of hippocampal long-term (LTP) requires protein and mRNA synthesis, suggesting that neuronal activity resulting in LTP initiates a cascade of gene expression. The expression of the gene for the extracellular serine protease tissue plasminogen activator (t-PA) is induced during LTP. Here we analyze long-lasting LTP (L-LTP,>4 hr)in CA1 hippocampal slices of mice homozygous for disrupted t-PA genes. Although mutant mice appear to exhibit long-term potentiation, we provide evidence that these mice are devoid of conventional homosynaptic L-LTP at the Schaffer collateral-CA1 pyramidal cell synapse. Most remarkably, t-PA-deficient mice exhibit a different form of long-lasting potentiation that is characterized by an NMDA receptor-dependent modification of GABA transmission in the CA1 region.
Frey
U
U
Federal Institute for Neurobiology, Magdeburg, Germany.
Müller
M
M
Kuhl
D
D
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D015870:Gene Expression; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D010641:Phenotype; D010852:Picrotoxin / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015763:2-Amino-5-phosphonovalerate; D018756:GABA Antagonists; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; D010959:Tissue Plasminogen Activator; D005680:gamma-Aminobutyric Acid