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Normal cognitive and social development require posterior cerebellar activity
Open accessAbstract
Cognitive and social capacities require postnatal experience, yet the pathways by which experience guides development are unknown. Here we show that the normal development of motor and nonmotor capacities requires cerebellar activity. Using chemogenetic perturbation of molecular layer interneurons to attenuate cerebellar output in mice, we found that activity of posterior regions in juvenile life modulates adult expression of eyeblink conditioning (paravermal lobule VI, crus I), reversal learning (lobule VI), persistive behavior and novelty-seeking (lobule VII), and social preference (crus I/II). Perturbation in adult life altered only a subset of phenotypes. Both adult and juvenile disruption left gait metrics largely unaffected. Contributions to phenotypes increased with the amount of lobule inactivated. Using an anterograde transsynaptic tracer, we found that posterior cerebellum made strong connections with prelimbic, orbitofrontal, and anterior cingulate cortex. These findings provide anatomical substrates for the clinical observation that cerebellar injury increases the risk of autism.
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“One cerebellar domain that has been implicated in ASD is the posterior cerebellar vermis6,7,32.”
From Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits (2020) · cites this paper as [32]
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Metadata
- Authors
- Badura, A., Verpeut, J. L., Metzger, J. W., Pereira, T. D., Pisano, T. J., Deverett, B., Bakshinskaya, D. E., & Wang, S. S.-H.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Princeton University (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Wang, Samuel S-H
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-09-20
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6195348
- OpenAlex
- W2889806840
- Cited by
- 205
- References
- 76
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 32 · 2023: 33 · 2022: 27 · 2021: 30 · 2020: 27 · 2019: 14
- FWCI
- 10.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion, other-oa)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Innovational Research Incentives Scheme VENI (NWO,ZonMw))
- Nancy Lurie Marks Family Foundation
- National Institutes of Health (R01 NS045193, R01 MH115750, F30 MH115577, F31 NS089303)
- New Jersey Commission on Brain Injury Research (CBIR16FEL010)
- National Science Foundation (Graduate Research Fellowship DGE-1148900)
- Rutgers Robert Wood Johnson Medical School-Princeton University M.D.-Ph.D. Program
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- posterior cerebellum, cerebellar development, molecular layer interneurons, eyeblink conditioning, reversal learning, social preferences, novelty seeking, orbitofrontal cortex, anterior cingulate cortex, prelimbic cortex, autism risk, postnatal experience, gait
- MeSH terms
- Animals, Autistic Disorder, Behavior, Animal, Brain Mapping, Cerebellum, Cognition, Disease Models, Animal, Humans, Image Processing, Computer-Assisted, Interneurons, Learning, Magnetic Resonance Imaging, Neural Pathways, Social Change, Mice
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