| Autor: |
Veleanu M; Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, 75005 Paris, France., Urrieta-Chávez B; Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, 75005 Paris, France., Sigoillot SM; Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, 75005 Paris, France., Paul MA; Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, 75005 Paris, France., Usardi A; Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, 75005 Paris, France., Iyer K; Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, 75005 Paris, France., Delagrange M; Plateforme qPCR-Haut Débit-Genomic Paris Centre, Institut de Biologie de l'Ecole Normale Supérieure, 75005 Paris, France., Doyle JP; Laboratory of Molecular Biology, The Rockefeller University, New York, NY 10065.; HHMI, The Rockefeller University, New York, NY 10065., Heintz N; Laboratory of Molecular Biology, The Rockefeller University, New York, NY 10065.; HHMI, The Rockefeller University, New York, NY 10065., Bécamel C; Institute for Functional Genomics, University of Montpellier, CNRS, INSERM, 34094 Montpellier, France., Selimi F; Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, 75005 Paris, France. |
| Abstrakt: |
Environmental perturbations during the first years of life are a major factor in psychiatric diseases. Phencyclidine (PCP), a drug of abuse, has psychomimetic effects, and neonatal subchronic administration of PCP in rodents leads to long-term behavioral changes relevant for schizophrenia. The cerebellum is increasingly recognized for its role in diverse cognitive functions. However, little is known about potential cerebellar changes in models of schizophrenia. Here, we analyzed the characteristics of the cerebellum in the neonatal subchronic PCP model. We found that, while the global cerebellar cytoarchitecture and Purkinje cell spontaneous spiking properties are unchanged, climbing fiber/Purkinje cell synaptic connectivity is increased in juvenile mice. Neonatal subchronic administration of PCP is accompanied by increased cFos expression, a marker of neuronal activity, and transient modification of the neuronal surfaceome in the cerebellum. The largest change observed is the overexpression of Ctgf, a gene previously suggested as a biomarker for schizophrenia. This neonatal increase in Ctgf can be reproduced by increasing neuronal activity in the cerebellum during the second postnatal week using chemogenetics. However, it does not lead to increased climbing fiber/Purkinje cell connectivity in juvenile mice, showing the complexity of PCP action. Overall, our study shows that administration of the drug of abuse PCP during the developmental period of intense cerebellar synaptogenesis and circuit remodeling has long-term and specific effects on Purkinje cell connectivity and warrants the search for this type of synaptic changes in psychiatric diseases. |
