RIM1alpha and interacting proteins involved in presynaptic plasticity mediate prepulse inhibition and additional behaviors linked to schizophrenia.
Several presynaptic proteins involved in neurotransmitter release in the CNS have been implicated in schizophrenia in human clinical genetic studies, in postmortem studies, and in studies of putative animal models of schizophrenia. The presynaptic protein RIM1alpha mediates presynaptic plasticity and cognitive function. We now demonstrate that mice deficient in RIM1alpha exhibit abnormalities in multiple schizophrenia-relevant behavioral tasks including prepulse inhibition, response to psychotomimetic drugs, and social interaction. These schizophrenia-relevant behavioral findings are relatively selective to RIM1alpha-deficient mice, as mice bearing mutations in the RIM1alpha binding partners Rab3A or synaptotagmin 1 only show decreased prepulse inhibition. In addition to RIM1alpha's involvement in multiple behavioral abnormalities, these data suggest that alterations in presynaptic forms of short-term plasticity are linked to alterations in prepulse inhibition, a measure of sensorimotor gating.
Blundell
Jacqueline
J
Departments of Neurology and Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-8813, USA.
Kaeser
Pascal S
PS
Südhof
Thomas C
TC
Powell
Craig M
CM
D000818:Animals; D003071:Cognition / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006213:Hallucinogens / Q000494:pharmacology; D007175:Impulsive Behavior / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology; D012919:Social Behavior; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D006213:Hallucinogens; C491490:Rims1 protein, mouse; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D016291:Dizocilpine Maleate; D019204:GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein
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