RIM1alpha is required for presynaptic long-term potentiation.
Two main forms of long-term potentiation (LTP)-a prominent model for the cellular mechanism of learning and memory-have been distinguished in the mammalian brain. One requires activation of postsynaptic NMDA (N-methyl d-aspartate) receptors, whereas the other, called mossy fibre LTP, has a principal presynaptic component. Mossy fibre LTP is expressed in hippocampal mossy fibre synapses, cerebellar parallel fibre synapses and corticothalamic synapses, where it apparently operates by a mechanism that requires activation of protein kinase A. Thus, presynaptic substrates of protein kinase A are probably essential in mediating this form of long-term synaptic plasticity. Studies of knockout mice have shown that the synaptic vesicle protein Rab3A is required for mossy fibre LTP, but the protein kinase A substrates rabphilin, synapsin I and synapsin II are dispensable. Here we report that mossy fibre LTP in the hippocampus and the cerebellum is abolished in mice lacking RIM1alpha, an active zone protein that binds to Rab3A and that is also a protein kinase A substrate. Our results indicate that the long-term increase in neurotransmitter release during mossy fibre LTP may be mediated by a unitary mechanism that involves the GTP-dependent interaction of Rab3A with RIM1alpha at the interface of synaptic vesicles and the active zone.
Castillo
Pablo E
PE
Nancy Friend Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94304, USA.
Schoch
Susanne
S
Schmitz
Frank
F
Südhof
Thomas C
TC
Malenka
Robert C
RC
D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D019204:GTP-Binding Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology*; D011689:Purkinje Cells / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C107293:Rim protein, mammalian; C491490:Rims1 protein, mouse; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins