Normal cognitive and social development require posterior cerebellar activity

Badura, Aleksandra; Verpeut, Jessica L; Metzger, Julia W; Pereira, Talmo D; Pisano, Thomas J; Deverett, Ben; Bakshinskaya, Dariya E; Wang, Samuel S-H

doi:10.7554/elife.36401

Cited by 205Memory and Neural MechanismsMotor Control and AdaptationNeuroscience and Neuropharmacology Research

Normal cognitive and social development require posterior cerebellar activity

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Badura, Aleksandra, Verpeut, Jessica L, Metzger, Julia W, Pereira, Talmo D, Pisano, Thomas J, Deverett, Ben, Bakshinskaya, Dariya E, Wang, Samuel S-H·2018·eLife

DOI 10.7554/elife.36401PMC PMC6195348

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Abstract

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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The posterior cerebellar vermis is implicated in ASD.
“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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The cerebellum is involved in processing of predictions and prediction errors in a fear conditioning paradigm
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A Data Driven Approach Reveals That Anomalous Motor System Connectivity is Associated With the Severity of Core Autism Symptoms
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A FN-MdV pathway and its role in cerebellar multimodular control of sensorimotor behavior
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Atypical cerebellar functional connectivity at 9 months of age predicts delayed socio‐communicative profiles in infants at high and low risk for autism
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Cerebellar-Cortical Connectivity Is Linked to Social Cognition Trans-Diagnostically
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The p75NTR Influences Cerebellar Circuit Development and Adult Behavior via Regulation of Cell Cycle Duration of Granule Cell Progenitors
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The Optogenetic Revolution in Cerebellar Investigations
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The resting-state cerebro-cerebellar function connectivity and associations with verbal working memory performance
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Phylogenetic comparative analysis of the cerebello-cerebral system in 34 species highlights primate-general expansion of cerebellar crura I-II
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Converging and Diverging Cerebellar Pathways for Motor and Social Behaviors in Mice
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Family history of depression is associated with alterations in task‐dependent connectivity between the cerebellum and ventromedial prefrontal cortex
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Social behavior in prepubertal neurexin 1α deficient rats: A model of neurodevelopmental disorders.
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Adeno-associated virus (AAV) reduces cortical dendritic complexity in a TLR9-dependent mannerPreprint
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The Cerebellum Is Related to Cognitive Dysfunction in White Matter Hyperintensities
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Activated PI3Kδ syndrome, an immunodeficiency disorder, leads to sensorimotor deficits recapitulated in a murine model
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Transcriptome programs involved in the development and structure of the cerebellum
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The cerebellum gains weight: A systematic review of alterations in cerebellar volume and cerebro-cerebellar functional alterations in individuals with eating disorders
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Purkinje-cell-specific MeCP2 deficiency leads to motor deficits and autistic-like behavior due to aberrations in PTP1B-TrkB-SK signaling
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4E-BP2-dependent translation in cerebellar Purkinje cells controls spatial memory but not autism-like behaviors
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Sensory Over-responsivity and Aberrant Plasticity in Cerebellar Cortex in a Mouse Model of Syndromic Autism
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DESARROLLO DE LA ALTA CAPACIDAD DURANTE LA INFANCIA TEMPRANA
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Adolescent treadmill exercise enhances hippocampal brain-derived neurotrophic factor (BDNF) expression and improves cognition in autism-modeled rats
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Modified climbing fiber/Purkinje cell synaptic connectivity in the cerebellum of the neonatal phencyclidine model of schizophrenia
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Serotonergic Input into the Cerebellar Cortex Modulates Anxiety-Like Behavior
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Self-citation

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: Badura, Aleksandra
Verpeut, Jessica L
Metzger, Julia W
Pereira, Talmo D
Pisano, Thomas J
Deverett, Ben
Bakshinskaya, Dariya E
Wang, Samuel S-H
Venue: eLife
Publisher: eLife Sciences Publications, Ltd
Published: 2018-09-20
Volume: 7
ISSN: 2050-084X (ISSN-L)
DOI: 10.7554/elife.36401
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 · 2017: 1
FWCI: 10.57
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
creativecommons.org/licenses/by/4.0/ (am)
creativecommons.org/licenses/by/4.0/ (tdm)
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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Normal cognitive and social development require posterior cerebellar activity

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