Normal cognitive and social development require posterior cerebellar activity

Author:

Badura Aleksandra1234ORCID,Verpeut Jessica L13ORCID,Metzger Julia W13ORCID,Pereira Talmo D13ORCID,Pisano Thomas J135,Deverett Ben135ORCID,Bakshinskaya Dariya E13,Wang Samuel S-H13ORCID

Affiliation:

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.

Funder

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Nancy Lurie Marks Family Foundation

National Institutes of Health

New Jersey Commission on Brain Injury Research

National Science Foundation

Rutgers Robert Wood Johnson Medical School-Princeton University M.D.-Ph.D. Program

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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