Compromised Survival of Cerebellar Molecular Layer Interneurons Lacking GDNF Receptors GFRα1 or RET Impairs Normal Cerebellar Motor Learning

Cell Reports

Stefanos Stagkourakis¹  Carlos F. Ibáñez¹  Maria Christina Sergaki¹  Christian Broberger¹  Agnès Gruart²  Juan Carlos López-Ramos²  José María Delgado-García² 

[1] Department of Neuroscience, Karolinska Institute, Stockholm S-17177, Sweden;Division of Neurosciences, Pablo de Olavide University, Seville 41013, Spain;

关键词: cerebellum;    eyeblink conditioning;    neuronal migration;    Purkinje cell;    synaptic inhibition;    vestibulo-ocular reflex;   

DOI  :  10.1016/j.celrep.2017.05.030

来源: DOAJ

【 摘 要 】

The role of neurotrophic factors as endogenous survival proteins for brain neurons remains contentious. In the cerebellum, the signals controlling survival of molecular layer interneurons (MLIs) are unknown, and direct evidence for the requirement of a full complement of MLIs for normal cerebellar function and motor learning has been lacking. Here, we show that Purkinje cells (PCs), the target of MLIs, express the neurotrophic factor GDNF during MLI development and survival of MLIs depends on GDNF receptors GFRα1 and RET. Conditional mutant mice lacking either receptor lose a quarter of their MLIs, resulting in compromised synaptic inhibition of PCs, increased PC firing frequency, and abnormal acquisition of eyeblink conditioning and vestibulo-ocular reflex performance, but not overall motor activity or coordination. These results identify an endogenous survival mechanism for MLIs and reveal the unexpected vulnerability and selective requirement of MLIs in the control of cerebellar-dependent motor learning.

【 授权许可】

Unknown