Cerebellar structure and function abnormalities in 16p11.2 microduplication mice
Cessily Hayes1,2,3, Hunter Halverson1,2, Krisha Keeran1
1Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA.
Brain Communications
|May 18, 2026
Summary
16p11.2 microduplication in mice shows specific cerebellar lobule VI abnormalities, impacting associative learning. These findings may illuminate the cerebellar role in neuropsychiatric disorders like schizophrenia.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- 16p11.2 microduplication is linked to neuropsychiatric disorders, with cerebellar abnormalities implicated.
- Previous studies show cerebellar transcriptional dysregulation and reduced volume in 16p11.2 duplication models.
Purpose of the Study:
- To characterize cerebellar anatomy and function in 16p11.2 microduplication (16p11.2dp/+) mice.
- To investigate the impact of 16p11.2 microduplication on cerebellar-dependent learning.
Main Methods:
- Histological examination of the cerebellar cortex in 16p11.2dp/+ mice.
- Assessment of gait, motor coordination, and delay eyeblink conditioning.
Main Results:
- No structural differences or motor impairments were found in cerebellar lobule IV/V.
- Increased Purkinje cell (PC) mislocalization and decreased parvalbumin in molecular layer interneurons (MLIs) were observed in lobule VI.
- 16p11.2dp/+ mice exhibited deficits in conditioned response percentage and onset latency during delay eyeblink conditioning.
Conclusions:
- Lobule VI-specific alterations in PC localization and MLI parvalbumin expression may underlie impaired associative learning in 16p11.2dp/+ mice.
- These findings suggest a potential role for cerebellar dysfunction in the pathogenesis of neuropsychiatric disorders associated with 16p11.2 microduplication.
