The presynaptic active zone protein RIM1alpha is critical for normal learning and memory.
The active zone protein RIM1alpha is required both for maintaining normal probability of neurotransmitter release and for long-term presynaptic potentiation at brain synapses. We now demonstrate that RIM1alpha(-/-) mice exhibit normal coordination and anxiety-related behaviors but display severely impaired learning and memory. Mice with a synaptotagmin 1 mutation, which selectively lowers release probability, and mice with Rab3A deletion, which selectively abolishes presynaptic long-term potentiation, do not exhibit this abnormality. Our data suggest that a decrease in release probability or a loss of presynaptic LTP alone is not sufficient to cause major behavioral alterations, but the combination of presynaptic abnormalities in RIM1alpha(-/-) mice severely alters learning and memory.
Powell
Craig M
CM
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. craig.powell@utsouthwestern.edu
Schoch
Susanne
S
Monteggia
Lisa
L
Barrot
Michel
M
Matos
Maria F
MF
Feldmann
Nicole
N
Südhof
Thomas C
TC
Nestler
Eric J
EJ
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins; D003214:Conditioning, Classical / Q000502:physiology; D005239:Fear / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D017403:In Situ Hybridization / Q000379:methods; D007858:Learning / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000235:genetics; D013028:Space Perception / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology; D050863:Synaptotagmin I; D050857:Synaptotagmins; D013997:Time Factors; D020826:rab3A GTP-Binding Protein / Q000502:physiology
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C107293:Rim protein, mammalian; C491490:Rims1 protein, mouse; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D050857:Synaptotagmins; D019204:GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein