ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2025
Adolescent Cerebellar Nuclei Manipulation Alters Reversal Learning and Perineuronal Net Intensity Independently in Male and Female Mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Altered Brain Extracellular Matrix Structure and Sex-Specific Learning/Memory Dysfunction in Mice Lacking the Functional Amyloid Cystatin-Related Epididymal Spermatogenic (CRES).bioRxiv : the preprint server for biology · 2026Article
- Attenuation of social preference and alteration of cortical neurons following adolescent cerebellar nuclei perturbation.Molecular psychiatry · 2026Article
- Brain-wide mapping of developmental trajectories of cerebellar efferent projections.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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2 authors.
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Abstract
The cerebellum, identified to be active during cognitive and social behavior, has multisynaptic connections through the cerebellar nuclei (CN) and thalamus to cortical regions, yet formation and modulation of these pathways are not fully understood. Perineuronal nets (PNNs) respond to changes in local cellular activity and emerge during development. PNNs are implicated in learning and neurodevelopmental disorders, but their role in the CN during development is unknown. Connectivity deficits, specifically between lateral CN (LCN) and cortical regions have been found in autism spectrum disorder with patients displaying reduced cognitive flexibility. To examine the role of LCN on cognition, neural activity was perturbed in both male and female mice using designer receptors exclusively activated by designer drugs (DREADDs) from postnatal day 21 to 35. We found that while an adolescent LCN disruption did not alter task acquisition, correct choice reversal performance was dependent on DREADD manipulation and sex. Inhibitory DREADDs improved reversal learning in males (5 d faster to criteria), and excitatory DREADDs improved female reversal learning (10 d faster to criteria) compared with controls. Interestingly, the DREADD manipulation in females regardless of direction reduced PNN intensity, whereas in males, only the inhibitory DREADDs reduced PNNs. This suggests a chronic adolescent LCN manipulation may have sex-specific compensatory changes in PNN structure and LCN output to improve reversal learning. This study provides new evidence for LCN in nonmotor functions and sex-dependent differences in behavior and CN plasticity.
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