Neonatal brain injury causes cerebellar learning deficits and Purkinje cell dysfunction.
Document Type
Journal Article
Publication Date
8-13-2018
Journal
Nat Commun
Volume
9
Issue
1
Inclusive Pages
3235
DOI
10.1038/s41467-018-05656-w
Abstract
Premature infants are more likely to develop locomotor disorders than term infants. In a chronic sub-lethal hypoxia (Hx) mouse model of neonatal brain injury, we recently demonstrated the presence of cellular and physiological changes in the cerebellar white matter. We also observed Hx-induced delay in Purkinje cell (PC) arborization. However, the behavioral consequences of these cellular alterations remain unexplored. Using the Erasmus Ladder to study cerebellar behavior, we report the presence of locomotor malperformance and long-term cerebellar learning deficits in Hx mice. Optogenetics experiments in Hx mice reveal a profound reduction in spontaneous and photoevoked PC firing frequency. Finally, treatment with a gamma-aminobutyric acid (GABA) reuptake inhibitor partially rescues locomotor performance and improves PC firing. Our results demonstrate a long-term miscoordination phenotype characterized by locomotor malperformance and cerebellar learning deficits in a mouse model of neonatal brain injury. Our findings also implicate the developing GABA network as a potential therapeutic target for prematurity-related locomotor deficits.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Sathyanesan, A., Kundu, S., Abbah, J., & Gallo, V. (2018). Neonatal brain injury causes cerebellar learning deficits and Purkinje cell dysfunction.. Nat Commun, 9 (1). http://dx.doi.org/10.1038/s41467-018-05656-w
Peer Reviewed
1
Open Access
1
