TY - JOUR
T1 - RIM1α is required for presynaptic long-term potentiation
AU - Castillo, Pablo E.
AU - Schoch, Susanne
AU - Schmitz, Frank
AU - Südhof, Thomas C.
AU - Malenka, Robert C.
N1 - Funding Information:
We thank H. Riedesel for help with the RIM1a knockout mice. This study was supported by grants from the NIH (R.C.M.).
PY - 2002/1/17
Y1 - 2002/1/17
N2 - 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 RIM1α, 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 RIM1α at the interface of synaptic vesicles and the active zone.
AB - 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 RIM1α, 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 RIM1α at the interface of synaptic vesicles and the active zone.
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U2 - 10.1038/415327a
DO - 10.1038/415327a
M3 - Article
C2 - 11797010
AN - SCOPUS:0037122459
SN - 0028-0836
VL - 415
SP - 327
EP - 330
JO - Nature
JF - Nature
IS - 6869
ER -