Normal cognitive and social development require posterior cerebellar activity
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 t...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/36401 |
| _version_ | 1818028431671033856 |
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| author | Aleksandra Badura Jessica L Verpeut Julia W Metzger Talmo D Pereira Thomas J Pisano Ben Deverett Dariya E Bakshinskaya Samuel S-H Wang |
| author_facet | Aleksandra Badura Jessica L Verpeut Julia W Metzger Talmo D Pereira Thomas J Pisano Ben Deverett Dariya E Bakshinskaya Samuel S-H Wang |
| author_sort | Aleksandra Badura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:03:41Z |
| format | Article |
| id | doaj.art-1f2dd36d64b84f80ae27f05c6db943d3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:03:41Z |
| publishDate | 2018-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1f2dd36d64b84f80ae27f05c6db943d32022-12-22T02:01:18ZengeLife Sciences Publications LtdeLife2050-084X2018-09-01710.7554/eLife.36401Normal cognitive and social development require posterior cerebellar activityAleksandra Badura0https://orcid.org/0000-0002-0119-5108Jessica L Verpeut1https://orcid.org/0000-0003-2941-7697Julia W Metzger2https://orcid.org/0000-0002-6380-8141Talmo D Pereira3https://orcid.org/0000-0001-9075-8365Thomas J Pisano4Ben Deverett5https://orcid.org/0000-0002-3119-7649Dariya E Bakshinskaya6Samuel S-H Wang7https://orcid.org/0000-0002-0490-9786Princeton Neuroscience Institute, Princeton University, Princeton, United States; Netherlands Institute for Neuroscience, Amsterdam, The Netherlands; Department of Molecular Biology, Princeton University, Princeton, United States; Department of Neuroscience, Erasmus MC, Rotterdam, The NetherlandsPrinceton Neuroscience Institute, Princeton University, Princeton, United States; Department of Molecular Biology, Princeton University, Princeton, United StatesPrinceton Neuroscience Institute, Princeton University, Princeton, United States; Department of Molecular Biology, Princeton University, Princeton, United StatesPrinceton Neuroscience Institute, Princeton University, Princeton, United States; Department of Molecular Biology, Princeton University, Princeton, United StatesPrinceton Neuroscience Institute, Princeton University, Princeton, United States; Department of Molecular Biology, Princeton University, Princeton, United States; Robert Wood Johnson Medical School, New Brunswick, United StatesPrinceton Neuroscience Institute, Princeton University, Princeton, United States; Department of Molecular Biology, Princeton University, Princeton, United States; Robert Wood Johnson Medical School, New Brunswick, United StatesPrinceton Neuroscience Institute, Princeton University, Princeton, United States; Department of Molecular Biology, Princeton University, Princeton, United StatesPrinceton Neuroscience Institute, Princeton University, Princeton, United States; Department of Molecular Biology, Princeton University, Princeton, United StatesCognitive 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.https://elifesciences.org/articles/36401cerebellumdevelopmenttranssynapticcognitivechemogeneticflexible behavior |
| spellingShingle | Aleksandra Badura Jessica L Verpeut Julia W Metzger Talmo D Pereira Thomas J Pisano Ben Deverett Dariya E Bakshinskaya Samuel S-H Wang Normal cognitive and social development require posterior cerebellar activity eLife cerebellum development transsynaptic cognitive chemogenetic flexible behavior |
| title | Normal cognitive and social development require posterior cerebellar activity |
| title_full | Normal cognitive and social development require posterior cerebellar activity |
| title_fullStr | Normal cognitive and social development require posterior cerebellar activity |
| title_full_unstemmed | Normal cognitive and social development require posterior cerebellar activity |
| title_short | Normal cognitive and social development require posterior cerebellar activity |
| title_sort | normal cognitive and social development require posterior cerebellar activity |
| topic | cerebellum development transsynaptic cognitive chemogenetic flexible behavior |
| url | https://elifesciences.org/articles/36401 |
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