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Elife. 2018 Sep 20;7. pii: e36401. doi: 10.7554/eLife.36401.

Normal cognitive and social development require posterior cerebellar activity.

Author information

1
Princeton Neuroscience Institute, Princeton University, Princeton, United States.
2
Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.
3
Department of Molecular Biology, Princeton University, Princeton, United States.
4
Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands.
5
Robert Wood Johnson Medical School, New Brunswick, United States.

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.

KEYWORDS:

cerebellum; chemogenetic; cognitive; development; flexible behavior; mouse; neuroscience; transsynaptic

PMID:
30226467
PMCID:
PMC6195348
DOI:
10.7554/eLife.36401
[Indexed for MEDLINE]
Free PMC Article

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