Abstract:
: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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Sergaki MC,López-Ramos JC,Stagkourakis S,Gruart A,Broberger C,Delgado-García JM,Ibáñez CFdoi
10.1016/j.celrep.2017.05.030subject
Has Abstractpub_date
2017-06-06 00:00:00pages
1977-1986issue
10issn
2211-1247pii
S2211-1247(17)30672-1journal_volume
19pub_type
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