Normal cognitive and social development require posterior cerebellar activity
- Princeton University, 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.
Data availability
Code and data for the main figures are available via the GitHub repository https://github.com/wanglabprinceton/behavioral-development.The complete raw data for this study are available from the corresponding author upon request (including behavioral videos and serial two-photon tomographic brain images of each mouse).
Article and author information
Author details
Funding
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Innovational Research Incentives Scheme VENI (NWO ZonMw))
- Aleksandra Badura
Nancy Lurie Marks Family Foundation
- Samuel S-H Wang
National Institutes of Health (R01 NS045193)
- Samuel S-H Wang
New Jersey Commission on Brain Injury Research (CBIR16FEL010)
- Jessica L Verpeut
National Science Foundation (Graduate Research Fellowship DGE-1148900)
- Talmo D Pereira
Rutgers Robert Wood Johnson Medical School-Princeton University M.D.-Ph.D. Program
- Thomas J Pisano
- Ben Deverett
National Institutes of Health (R01 MH115750)
- Samuel S-H Wang
National Institutes of Health (F30 MH115577)
- Ben Deverett
National Institutes of Health (F31 NS089303)
- Thomas J Pisano
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experimental procedures were approved by the Princeton University Institutional Animal Care and Use Committee (protocol number: 1943-16) and performed in accordance with the animal welfare guidelines of the National Institutes of Health. All mice were housed in Optimice cages (Animal Care Systems, Centennial, CO) containing blended bedding (The Andersons, Maumee, OH), paper nesting strips, and one heat-dried virgin pulp cardboard hut (Shepherd Specialty Papers, Milford, NJ). PicoLab Rodent Diet food pellets (LabDiet, St. Louis, MO) and drinking water (or CNO water in the developmental groups) were provided ad libitum. Mice were relocated to clean cages with new component materials every two weeks. All mice were group-housed in reverse light cycle to promote maximal performance during behavioral testing. All surgery was performed under isoflurane anesthesia (5% for induction, 1-2% in oxygen; 1 L/min) and daily monitoring was employed to minimize suffering.
Copyright
© 2018, Badura et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Normal cognitive and social development require posterior cerebellar activity
eLife 7:e36401.
https://doi.org/10.7554/eLife.36401
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