4.8 Article

Normal cognitive and social development require posterior cerebellar activity

Journal

ELIFE
Volume 7, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.36401

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Funding

  1. Nederlandse Organisatie voor Wetenschappelijk Onderzoek Innovational Research Incentives Scheme VENI (NWO,ZonMw)
  2. Nancy Lurie Marks Family Foundation
  3. National Institutes of Health [R01 NS045193, R01 MH115750, F30 MH115577, F31 NS089303]
  4. New Jersey Commission on Brain Injury Research [CBIR16FEL010]
  5. National Science Foundation [DGE-1148900]
  6. Rutgers Robert Wood Johnson Medical School-Princeton University M.D.-Ph.D. Program

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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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