Modified climbing fiber/Purkinje cell synaptic connectivity in the cerebellum of the neonatal phencyclidine model of schizophrenia
M. Veleanu, Beetsi Urrieta-Chávez, Séverine M. Sigoillot, Maela A. Paul, A. Usardi, Keerthana Iyer, Marine Delagrange, J. Doyle, N. Heintz, C. Bécamel, F. Selimi
Proceedings of the National Academy of Sciences of the United States of America May 19, 2022 DOI: 10.1073/pnas.2122544119 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal model study (rodent) Peer reviewed |
|---|---|
| Population | Neonatal rodents (likely rats or mice, not specified) |
| Intervention | Phencyclidine |
| Key points | Subchronic neonatal phencyclidine administration in rodents caused long-term synaptic changes in Purkinje cells and transient cerebellar gene expression changes. Chemogenetic activation of cerebellar neurons reproduced some molecular but not the long-term synaptic effects, indicating a complex mechanism and suggesting cerebellar defects may contribute to psychiatric disease. |
Abstract
Significance Synaptogenesis and neural network remodeling are at their maximum during the perinatal period of human brain development. Perturbations of this highly sensitive stage might underlie the etiology of neurodevelopmental disorders. Subchronic neonatal administration of phencyclidine, a drug of abuse, has been used to model schizophrenia in rodents. In this model, we found specific long-term synaptic changes in Purkinje cells and transient gene expression changes in the cerebellum. While transient increased neuronal activity in the cerebellum, induced using chemogenetics, reproduces some phencyclidine-induced molecular changes, it is insufficient to reproduce the long-term synaptic effects. Our results show the complex mechanism of action of phencyclidine on the development of neuronal connectivity and further highlight the potential contribution of cerebellar defects in psychiatric diseases.
Citations in the library
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