Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome.

TitleDeletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome.
Publication TypeJournal Article
Year of Publication2005
AuthorsKoekkoek, SKE, Yamaguchi, K, Milojkovic, BA, Dortland, BR, Ruigrok, TJH, Maex, R, De Graaf, W, Smit, AE, VanderWerf, F, Bakker, CE, Willemsen, R, Ikeda, T, Kakizawa, S, Onodera, K, Nelson, DL, Mientjes, E, Joosten, M, De Schutter, E, Oostra, BA, Ito, M, De Zeeuw, CI
JournalNeuron
Volume47
Issue3
Pagination339-52
Date Published2005 Aug 04
ISSN0896-6273
KeywordsAnimals, Cerebellum, Conditioning, Eyelid, Dendrites, Fragile X Mental Retardation Protein, Fragile X Syndrome, Gene Deletion, Humans, Long-Term Synaptic Depression, Male, Mice, Mice, Knockout, Mice, Mutant Strains, Models, Neurological, Nerve Fibers, Nerve Tissue Proteins, Purkinje Cells, Reflex, Startle, RNA-Binding Proteins
Abstract

Absence of functional FMRP causes Fragile X syndrome. Abnormalities in synaptic processes in the cerebral cortex and hippocampus contribute to cognitive deficits in Fragile X patients. So far, the potential roles of cerebellar deficits have not been investigated. Here, we demonstrate that both global and Purkinje cell-specific knockouts of Fmr1 show deficits in classical delay eye-blink conditioning in that the percentage of conditioned responses as well as their peak amplitude and peak velocity are reduced. Purkinje cells of these mice show elongated spines and enhanced LTD induction at the parallel fiber synapses that innervate these spines. Moreover, Fragile X patients display the same cerebellar deficits in eye-blink conditioning as the mutant mice. These data indicate that a lack of FMRP leads to cerebellar deficits at both the cellular and behavioral levels and raise the possibility that cerebellar dysfunctions can contribute to motor learning deficits in Fragile X patients.

DOI10.1016/j.neuron.2005.07.005
Alternate JournalNeuron
PubMed ID16055059
Grant List5 R01 HD38038 / HD / NICHD NIH HHS / United States