RT Journal Article
SR Electronic
T1 Mature Purkinje Cells Require the Retinoic Acid-Related Orphan Receptor-α (RORα) to Maintain Climbing Fiber Mono-Innervation and Other Adult Characteristics
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9546
OP 9562
DO 10.1523/JNEUROSCI.2977-12.2013
VO 33
IS 22
A1 Xiao Ru Chen
A1 Nicolas Heck
A1 Ann M. Lohof
A1 Christelle Rochefort
A1 Marie-Pierre Morel
A1 Rosine Wehrlé
A1 Mohamed Doulazmi
A1 Serge Marty
A1 Vidjeacoumary Cannaya
A1 Hasan X. Avci
A1 Jean Mariani
A1 Laure Rondi-Reig
A1 Guilan Vodjdani
A1 Rachel M. Sherrard
A1 Constantino Sotelo
A1 Isabelle Dusart
YR 2013
UL http://www.jneurosci.org/content/33/22/9546.abstract
AB Neuronal maturation during development is a multistep process regulated by transcription factors. The transcription factor RORα (retinoic acid-related orphan receptor α) is necessary for early Purkinje cell (PC) maturation but is also expressed throughout adulthood. To identify the role of RORα in mature PCs, we used Cre-lox mouse genetic tools in vivo that delete it specifically from PCs between postnatal days 10–21. Up to 14 d of age, differences between mutant and control PCs were not detectable: both were mono-innervated by climbing fibers (CFs) extending along their well-developed dendrites with spiny branchlets. By week 4, mutant mice were ataxic, some PCs had died, and remaining PC soma and dendrites were atrophic, with almost complete disappearance of spiny branchlets. The innervation pattern of surviving RORα-deleted PCs was abnormal with several immature characteristics. Notably, multiple functional CF innervation was reestablished on these mature PCs, simultaneously with the relocation of CF contacts to the PC soma and their stem dendrite. This morphological modification of CF contacts could be induced even later, using lentivirus-mediated depletion of rora from adult PCs. These data show that the late postnatal expression of RORα cell-autonomously regulates the maintenance of PC dendritic complexity, and the CF innervation status of the PC (dendritic vs somatic contacts, and mono-innervation vs multi-innervation). Thus, the differentiation state of adult neurons is under the control of transcription factors; and in their absence, adult neurons lose their mature characteristics and acquire some characteristics of an earlier developmental stage.