Normal cognitive and social development require posterior cerebellar activity.

TitleNormal cognitive and social development require posterior cerebellar activity.
Publication TypeJournal Article
Year of Publication2018
AuthorsBadura, A, Verpeut, JL, Metzger, JW, Pereira, TD, Pisano, TJ, Deverett, B, Bakshinskaya, DE, Wang, SS-H
JournalElife
Volume7
Date Published2018 09 20
ISSN2050-084X
KeywordsAnimals, Autistic Disorder, Behavior, Animal, Brain Mapping, Cerebellum, Cognition, Disease Models, Animal, Humans, Image Processing, Computer-Assisted, Interneurons, Learning, Magnetic Resonance Imaging, Mice, Neural Pathways, Social Change
Abstract

<p>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.</p>

DOI10.7554/eLife.36401
Alternate JournalElife
PubMed ID30226467
PubMed Central IDPMC6195348
Grant ListF31 NS089303 / NS / NINDS NIH HHS / United States
Innovational Research Incentives Scheme VENI (NWO,ZonMw) / / Nederlandse Organisatie voor Wetenschappelijk Onderzoek / International
F31 NS089303 / NH / NIH HHS / United States
R01 NS045193 / NH / NIH HHS / United States
Graduate Research Fellowship DGE-1148900 / / National Science Foundation / International
R01 MH115750 / MH / NIMH NIH HHS / United States
F30 MH115577 / NH / NIH HHS / United States
R01 NS045193 / NS / NINDS NIH HHS / United States
CBIR16FEL010 / / New Jersey Commission on Brain Injury Research / International
F30 MH115577 / MH / NIMH NIH HHS / United States
Innovational Research Incentives Scheme VENI (NWO ZonMw) / / Nederlandse Organisatie voor Wetenschappelijk Onderzoek / International
R01 MH115750 / NH / NIH HHS / United States