RIM1alpha and interacting proteins involved in presynaptic plasticity mediate prepulse inhibition and additional behaviors linked to schizophrenia.

Abstract	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.
Authors	Jacqueline Blundell, Pascal S Kaeser, Thomas C Südhof, Craig M Powell
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 30 Issue 15 Pg. 5326-33 (Apr 14 2010) ISSN: 1529-2401 [Electronic] United States
PMID	20392954 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Hallucinogens Rims1 protein, mouse Synaptotagmin I Syt1 protein, mouse Dizocilpine Maleate GTP-Binding Proteins rab3A GTP-Binding Protein
Topics	Animals Cognition (physiology) Dizocilpine Maleate (pharmacology) Female GTP-Binding Proteins (deficiency, genetics, metabolism) Hallucinogens (pharmacology) Impulsive Behavior (physiopathology) Male Mice Mice, Inbred C57BL Mice, Transgenic Motor Activity (drug effects, physiology) Mutation Neuronal Plasticity (physiology) Presynaptic Terminals (physiology) Psychomotor Performance (drug effects, physiology) Schizophrenia (physiopathology) Social Behavior Synaptotagmin I (genetics, metabolism) rab3A GTP-Binding Protein (genetics, metabolism)

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