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Cerebellar associative sensory learning defects in five mouse autism models

Author(s): Kloth, Alexander D; Badura, Aleksandra; Li, Amy; Cherskov, Adriana; Connolly, Sara G; et al

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Abstract: 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.
Publication Date: 9-Jul-2015
Citation: Kloth, Alexander D, Badura, Aleksandra, Li, Amy, Cherskov, Adriana, Connolly, Sara G, Giovannucci, Andrea, Bangash, M Ali, Grasselli, Giorgio, Pe nagarikano, 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. Elife, 4 (e06085 - e06085. doi:10.7554/eLife.06085
DOI: doi:10.7554/eLife.06085
ISSN: 2050-084X
Pages: e06085 - e06085
Type of Material: Journal Article
Journal/Proceeding Title: eLife
Version: Final published version. This is an open access article.

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