Dataset
Cerebellar structure and function abnormalities in 16p11.2 microduplication mice
University of Iowa
2025
DOI: 10.25820/data.008177
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 E Halverson - University of Iowa, PsychiatryKrisha Keeran - University of IowaKrislen Tison - University of IowaKamilla Jacobo - University of IowaAsriya Karki - Rutgers University–NewarkIsaias Herring - University of IowaSri Naga Swetha Tunuguntla - University of IowaMartha Pace - Upper Iowa UniversityBinh Doan - University of IowaHsiang M Wen - University of Iowa, PsychiatryAnnette J Klomp - University of IowaMarisol LaufferMarie E Gaine - University of Iowa, Pharmaceutical Sciences and Experimental TherapeuticsKrystal L Parker - University of Iowa, Iowa Neuroscience InstituteAislinn J Williams (Corresponding Author) - University of Iowa, Iowa Neuroscience Institute
- Contributors
- Brian Westra (Data Curator) - University of Iowa, Humanities and Social Sciences/Scholarly Impact
- Resource Type
- Dataset
- DOI
- 10.25820/data.008177
- Publisher
- University of Iowa
- Language
- English
- Date published
- 2025
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute; Humanities and Social Sciences/Scholarly Impact
- Record Identifier
- 9985034647002771
Metrics
1 File views/ downloads
2 Record Views