Journal article
Cerebellar structure and function abnormalities in 16p11.2 microduplication mice
Brain communications, Vol.8(3), fcag156
05/08/2026
DOI: 10.1093/braincomms/fcag156
Abstract
16p11.2 microduplication (16p11.2dp/+) is associated with neuropsychiatric disorders including schizophrenia, autism, and intellectual disability. Cerebellar abnormalities have been implicated in these disorders. In 16p11.2dp/+ mice, the cerebellum displays significant transcriptional dysregulation, and humans with 16p11.2 microduplication have decreased cerebellar volume. Despite this, cerebellar anatomy and cerebellar-dependent behavior in 16p11.2dp/+ mice remain uncharacterized. To address this, we histologically examined the cerebellar cortex in 16p11.2dp/+ mice. There were no structural differences in cerebellar lobule IV/V or impairments in gait or motor coordination, commonly associated with lobule IV/V. In contrast, more Purkinje cells (PCs) were mislocalized to the granule layer and parvalbumin expression was decreased in molecular layer interneurons (MLIs) in cerebellar lobule VI of 16p11.2dp/+ mice, but not in lobule IV/V. Cerebellar lobule VI is associated with delay eyeblink conditioning, and 16p11.2dp/+ mice are impaired in cerebellum-dependent associative learning on this task. Specifically, 16p11.2dp/+ mice had conditioned response (CR) percentage and CR onset latency deficits, suggesting lobule-specific alterations to PC localization and MLI parvalbumin expression may impair learning and adaptive timing of cerebellar-driven CRs. Similarly, schizophrenia involves CR acquisition deficits in delay eyeblink conditioning. Further investigation of the cerebellum in 16p11.2dp/+ mice may provide insights into the pathogenesis of neuropsychiatric disorders linked to this copy number variant.
Details
- Title: Subtitle
- Cerebellar structure and function abnormalities in 16p11.2 microduplication mice
- Creators
- Cessily Hayes - University of IowaHunter Halverson - University of IowaKrisha Keeran - University of IowaKrislen Tison - University of IowaKamilla Jacobo - University of IowaAsriya Karki - Rutgers, The State University of New JerseyIsaias Herring - University of IowaSri Naga Swetha Tunuguntla - University of IowaMartha Pace - Upper Iowa UniversityBinh Doan - University of IowaHsiang Wen - University of IowaAnnette Klomp - University of IowaMarisol Lauffer - University of IowaMarie E Gaine - University of IowaKrystal Parker - University of IowaAislinn J Williams - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Brain communications, Vol.8(3), fcag156
- DOI
- 10.1093/braincomms/fcag156
- ISSN
- 2632-1297
- eISSN
- 2632-1297
- Publisher
- Oxford University Press
- Grant note
- Iowa Neuroscience Institute Carver Trust Schizophrenia Research Program of Excellence Nellie Ball Collaborative
This project was funded by the Nellie Ball Research Trust Collaborative and the Iowa Neuroscience Institute Carver Trust Schizophrenia Research Program of Excellence.
- Language
- English
- Date published
- 05/08/2026
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9985163712902771
Metrics
1 Record Views