title: The presynaptic active zone protein RIM1alpha is critical for normal learning and memory.
abstract: 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.
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. craig.powell@utsouthwestern.edu
authors.forename: Craig M
authors.initials: CM
authors.lastname: Powell
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
authors.forename: Lisa
authors.initials: L
authors.lastname: Monteggia
authors.forename: Michel
authors.initials: M
authors.lastname: Barrot
authors.forename: Maria F
authors.initials: MF
authors.lastname: Matos
authors.forename: Nicole
authors.initials: N
authors.lastname: Feldmann
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: 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
chemical_list: 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