title: Region-specific deletions of RIM1 reproduce a subset of global RIM1α(-/-)  phenotypes.
abstract: The presynaptic protein RIM1α mediates multiple forms of presynaptic plasticity at both excitatory and inhibitory synapses. Previous studies of mice lacking RIM1α (RIM1α(-/-)  throughout the brain showed that deletion of RIM1α results in multiple behavioral abnormalities. In an effort to begin to delineate the brain regions in which RIM1 deletion mediates these abnormal behaviors, we used conditional (floxed) RIM1 knockout mice (fRIM1). By crossing these fRIM1 mice to previously characterized transgenic cre lines, we aimed to delete RIM1 selectively in the dentate gyrus (DG), using a specific preproopiomelanocortin promoter driving cre recombinase (POMC-cre) line , and in pyramidal neurons of the CA3 region of hippocampus, using the kainate receptor subunit 1 promoter driving cre recombinase (KA-cre). Neither of these cre driver lines was uniquely selective to the targeted regions. In spite of this, we were able to reproduce a subset of the global RIM1α(-/-)  behavioral abnormalities, thereby narrowing the brain regions in which loss of RIM1 is sufficient to produce these behavioral differences. Most interestingly, hypersensitivity to the pyschotomimetic MK-801 was shown in mice lacking RIM1 selectively in the DG, arcuate nucleus of the hypothalamus and select cerebellar neurons, implicating novel brain regions and neuronal subtypes in this behavior.
authors: Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors: M E
authors: ME
authors: Haws
authors: P S
authors: PS
authors: Kaeser
authors: D L
authors: DL
authors: Jarvis
authors: T C
authors: TC
authors: Südhof
authors: C M
authors: CM
authors: Powell
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics; D045442:Rotarod Performance Test; D055139:Sensory Gating / Q000187:drug effects / Q000235:genetics; D012919:Social Behavior; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: C491490:Rims1 protein, mouse; D016291:Dizocilpine Maleate; D019204:GTP-Binding Proteins