Behavioral flexibility in a mouse model of developmental cerebellar Purkinje cell loss
Open accessAbstract
Although behavioral inflexibility and Purkinje cell loss are both well established in autism, it is unknown if these phenomena are causally related. Using a mouse model, we tested the hypothesis that developmental abnormalities of the cerebellum, including Purkinje cell loss, result in behavioral inflexibility. Specifically, we made aggregation chimeras (Lc/+<-->+/+) between lurcher (Lc/+) mutant embryos and wildtype (+/+) control embryos. Lurcher mice lose 100% of their Purkinje cells postnatally, while chimeric mice lose varying numbers of Purkinje cells. We tested these mice on the acquisition and serial reversals of an operant conditional visual discrimination, a test of behavioral flexibility in rodents. During reversals 1 and 2, all groups of mice committed similar numbers of "perseverative" errors (those committed while session performance was <= 40% correct). Lurchers, however, committed a significantly greater number of "learning" errors (those committed while session performance was between 41% and 85% correct) than both controls and chimeras, and most were unable to advance past reversal 3. During reversals 3 and 4, chimeras, as a group, committed more "perseverative", but not "learning" errors than controls, although a comparison of Purkinje cell number and performance in individual mice revealed that chimeras with fewer Purkinje cells made more "learning" errors and had shorter response latencies than chimeras with more Purkinje cells. These data suggest that developmental cerebellar Purkinje cell loss may affect higher level cognitive processes which have previously been shown to be mediated by the prefrontal cortex, and are commonly deficient in autism spectrum disorders.
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Mice with reduced Purkinje cell numbers showed impaired performance on the later stages of a non-spatial serial reversal learning task.
“mice with reduced Purkinje cell numbers displayed impaired performance on the later stages of a non-spatial serial reversal learning task, a measure of behavioral flexibility [284],”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [284]
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- Authors
- Dickson, P. E., Rogers, T. D., Mar, N. D., Martin, L. A., Heck, D., Blaha, C. D., Goldowitz, D., & Mittleman, G.
- Affiliations
- University of Memphis (US)
- University of Tennessee Health Science Center (US)
- Azusa Pacific University (US)
- Corresponding author
- Mittleman, Guy
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 94
- Issue
- 2
- Pages
- 220-228
- ISSN
- 1074-7427 (ISSN-L)
- PMC
- PMC2922405
- OpenAlex
- W2031964842
- Cited by
- 59
- References
- 38
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 7 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 7 · 2012: 8
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Autism Speaks (AS1780)
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS063009)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Keywords
- behavioral flexibility, Purkinje cell degeneration, cerebellum, autism spectrum disorder, perseveration, reversal learning, cognitive flexibility, prefrontal cortex
- MeSH terms
- Analysis of Variance, Animals, Autistic Disorder, Behavior, Animal, Cell Count, Cerebellar Diseases, Cerebellum, Chimera, Conditioning, Operant, Discrimination Learning, Disease Models, Animal, Mice, Neurologic Mutants, Pattern Recognition, Visual, Photic Stimulation, Purkinje Cells, Reaction Time, Reversal Learning, Serial Learning, Cell Death, Mice, Executive Function
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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