Biological Sciences Division
Published July 9, 2015 | Version v1
Journal article Open

Cerebellar associative sensory learning defects in five mouse autism models

Creators

  • 1. Princeton University
  • 2. Johns Hopkins University
  • 3. University of Chicago
  • 4. University of California, Los Angeles
  • 5. Children's Hospital Boston
  • 6. RIKEN Brain Science Institute

Description

Sensory integration difficulties have been reported in autism, but their underlying braincircuit mechanisms are underexplored. Using five autism-related mouse models, Shank3+/ΔC, Mecp2R308/Y, Cntnap2−/−, L7-Tsc1 (L7/Pcp2Cre::Tsc1flox/+), 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/Pcp2Cre::Tsc1flox/+, which are associated with Purkinje-cell/deep-nuclear gene expression, along with Shank3+/ΔC. Amplitudes were smaller in L7/Pcp2Cre::Tsc1flox/+ as well as Shank3+/ΔC and Mecp2R308/Y, which are associated with granule cell pathway expression. Shank3+/ΔC and Mecp2R308/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.

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Additional details

Identifiers

DOI
10.7554/eLife.06085
Other
oai:uchicago.tind.io:9960

Funding

National Institute of Neurological Disorders and Stroke
R01 NS045193
National Institute of Mental Health
F31 MH098651
Simons Foundation
Autism Research Initiative
State of New Jersey Department of Health
New Jersey Commission on Brain Injury Research
Nancy Lurie Marks Family Foundation
Brain Research Foundation
Ministry of Education, Culture, Sports, Science, and Technology
Simons Foundation
Autism Research Initiative
Autism Speaks
Simons Foundation
Autism Research Initiative

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Neurobiology