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Cerebellar associative sensory learning defects in five mouse autism models
Sensory integration difficulties have been reported in autism, but their underlying brain-circuit mechanisms are underexplored. Using five autism-related mouse models, Shank3+/ΔC, Mecp2(R308/Y), Cntnap2−/−, L7-Tsc1 (L7/Pcp2(Cre)::Tsc1(flox/+)), and patDp(15q11-13)/+, we report specific perturbations...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512177/ https://www.ncbi.nlm.nih.gov/pubmed/26158416 http://dx.doi.org/10.7554/eLife.06085 |
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author | Kloth, Alexander D Badura, Aleksandra Li, Amy Cherskov, Adriana Connolly, Sara G Giovannucci, Andrea Bangash, M Ali Grasselli, Giorgio Peñagarikano, Olga Piochon, Claire Tsai, Peter T Geschwind, Daniel H Hansel, Christian Sahin, Mustafa Takumi, Toru Worley, Paul F Wang, Samuel S-H |
author_facet | Kloth, Alexander D Badura, Aleksandra Li, Amy Cherskov, Adriana Connolly, Sara G Giovannucci, Andrea Bangash, M Ali Grasselli, Giorgio Peñagarikano, Olga Piochon, Claire Tsai, Peter T Geschwind, Daniel H Hansel, Christian Sahin, Mustafa Takumi, Toru Worley, Paul F Wang, Samuel S-H |
author_sort | Kloth, Alexander D |
collection | PubMed |
description | Sensory integration difficulties have been reported in autism, but their underlying brain-circuit mechanisms are underexplored. Using five autism-related mouse models, Shank3+/ΔC, Mecp2(R308/Y), Cntnap2−/−, L7-Tsc1 (L7/Pcp2(Cre)::Tsc1(flox/+)), and patDp(15q11-13)/+, we report specific perturbations in delay eyeblink conditioning, a form of associative sensory learning requiring cerebellar plasticity. By distinguishing perturbations in the probability and characteristics of learned responses, we found that probability was reduced in Cntnap2−/−, patDp(15q11-13)/+, and L7/Pcp2(Cre)::Tsc1(flox/+), which are associated with Purkinje-cell/deep-nuclear gene expression, along with Shank3+/ΔC. Amplitudes were smaller in L7/Pcp2(Cre)::Tsc1(flox/+) as well as Shank3+/ΔC and Mecp2(R308/Y), which are associated with granule cell pathway expression. Shank3+/ΔC and Mecp2(R308/Y) also showed aberrant response timing and reduced Purkinje-cell dendritic spine density. Overall, our observations are potentially accounted for by defects in instructed learning in the olivocerebellar loop and response representation in the granule cell pathway. Our findings indicate that defects in associative temporal binding of sensory events are widespread in autism mouse models. DOI: http://dx.doi.org/10.7554/eLife.06085.001 |
format | Online Article Text |
id | pubmed-4512177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45121772015-07-27 Cerebellar associative sensory learning defects in five mouse autism models Kloth, Alexander D Badura, Aleksandra Li, Amy Cherskov, Adriana Connolly, Sara G Giovannucci, Andrea Bangash, M Ali Grasselli, Giorgio Peñagarikano, Olga Piochon, Claire Tsai, Peter T Geschwind, Daniel H Hansel, Christian Sahin, Mustafa Takumi, Toru Worley, Paul F Wang, Samuel S-H eLife Neuroscience Sensory integration difficulties have been reported in autism, but their underlying brain-circuit mechanisms are underexplored. Using five autism-related mouse models, Shank3+/ΔC, Mecp2(R308/Y), Cntnap2−/−, L7-Tsc1 (L7/Pcp2(Cre)::Tsc1(flox/+)), and patDp(15q11-13)/+, we report specific perturbations in delay eyeblink conditioning, a form of associative sensory learning requiring cerebellar plasticity. By distinguishing perturbations in the probability and characteristics of learned responses, we found that probability was reduced in Cntnap2−/−, patDp(15q11-13)/+, and L7/Pcp2(Cre)::Tsc1(flox/+), which are associated with Purkinje-cell/deep-nuclear gene expression, along with Shank3+/ΔC. Amplitudes were smaller in L7/Pcp2(Cre)::Tsc1(flox/+) as well as Shank3+/ΔC and Mecp2(R308/Y), which are associated with granule cell pathway expression. Shank3+/ΔC and Mecp2(R308/Y) also showed aberrant response timing and reduced Purkinje-cell dendritic spine density. Overall, our observations are potentially accounted for by defects in instructed learning in the olivocerebellar loop and response representation in the granule cell pathway. Our findings indicate that defects in associative temporal binding of sensory events are widespread in autism mouse models. DOI: http://dx.doi.org/10.7554/eLife.06085.001 eLife Sciences Publications, Ltd 2015-07-09 /pmc/articles/PMC4512177/ /pubmed/26158416 http://dx.doi.org/10.7554/eLife.06085 Text en © 2015, Kloth et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Kloth, Alexander D Badura, Aleksandra Li, Amy Cherskov, Adriana Connolly, Sara G Giovannucci, Andrea Bangash, M Ali Grasselli, Giorgio Peñagarikano, Olga Piochon, Claire Tsai, Peter T Geschwind, Daniel H Hansel, Christian Sahin, Mustafa Takumi, Toru Worley, Paul F Wang, Samuel S-H Cerebellar associative sensory learning defects in five mouse autism models |
title | Cerebellar associative sensory learning defects in five mouse autism models |
title_full | Cerebellar associative sensory learning defects in five mouse autism models |
title_fullStr | Cerebellar associative sensory learning defects in five mouse autism models |
title_full_unstemmed | Cerebellar associative sensory learning defects in five mouse autism models |
title_short | Cerebellar associative sensory learning defects in five mouse autism models |
title_sort | cerebellar associative sensory learning defects in five mouse autism models |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512177/ https://www.ncbi.nlm.nih.gov/pubmed/26158416 http://dx.doi.org/10.7554/eLife.06085 |
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