Cargando…
Region-specific deletions of RIM1 reproduce a subset of global RIM1α(−/−) phenotypes
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 del...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268893/ https://www.ncbi.nlm.nih.gov/pubmed/22103334 http://dx.doi.org/10.1111/j.1601-183X.2011.00755.x |
_version_ | 1782222424382636032 |
---|---|
author | Haws, M E Kaeser, P S Jarvis, D L Südhof, T C Powell, C M |
author_facet | Haws, M E Kaeser, P S Jarvis, D L Südhof, T C Powell, C M |
author_sort | Haws, M E |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3268893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-32688932012-11-26 Region-specific deletions of RIM1 reproduce a subset of global RIM1α(−/−) phenotypes Haws, M E Kaeser, P S Jarvis, D L Südhof, T C Powell, C M Genes Brain Behav Original Articles 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. Blackwell Publishing Ltd 2012-03 2012-01-13 /pmc/articles/PMC3268893/ /pubmed/22103334 http://dx.doi.org/10.1111/j.1601-183X.2011.00755.x Text en © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms |
spellingShingle | Original Articles Haws, M E Kaeser, P S Jarvis, D L Südhof, T C Powell, C M Region-specific deletions of RIM1 reproduce a subset of global RIM1α(−/−) phenotypes |
title | Region-specific deletions of RIM1 reproduce a subset of global RIM1α(−/−) phenotypes |
title_full | Region-specific deletions of RIM1 reproduce a subset of global RIM1α(−/−) phenotypes |
title_fullStr | Region-specific deletions of RIM1 reproduce a subset of global RIM1α(−/−) phenotypes |
title_full_unstemmed | Region-specific deletions of RIM1 reproduce a subset of global RIM1α(−/−) phenotypes |
title_short | Region-specific deletions of RIM1 reproduce a subset of global RIM1α(−/−) phenotypes |
title_sort | region-specific deletions of rim1 reproduce a subset of global rim1α(−/−) phenotypes |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268893/ https://www.ncbi.nlm.nih.gov/pubmed/22103334 http://dx.doi.org/10.1111/j.1601-183X.2011.00755.x |
work_keys_str_mv | AT hawsme regionspecificdeletionsofrim1reproduceasubsetofglobalrim1aphenotypes AT kaeserps regionspecificdeletionsofrim1reproduceasubsetofglobalrim1aphenotypes AT jarvisdl regionspecificdeletionsofrim1reproduceasubsetofglobalrim1aphenotypes AT sudhoftc regionspecificdeletionsofrim1reproduceasubsetofglobalrim1aphenotypes AT powellcm regionspecificdeletionsofrim1reproduceasubsetofglobalrim1aphenotypes |