Cerebellar brain-derived neurotrophic factor-trkB defect associated with impairment of eyeblink conditioning in stargazer mutant mice

Xiaoxi Qiao, Lu Chen, Hua Gao, Shaowen Bao, Franz Hefti, Richard F. Thompson, Beat Knusel

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

In the spontaneous ataxic mutant mouse stargazer, there is a selective reduction of brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebellum. BDNF protein levels in the cerebellum are reduced by 70%. Despite normal levels of full-length and truncated TrkB receptor, constitutive and neurotrophin-4/5-induced tyrosine phosphorylation was significantly reduced in several signal transduction molecules, including phospholipase-Cγ1, erk1, and erk2. Morphological examination revealed an increased number of external granule cells at postnatal day 15 and the presence of abnormal neurons resembling immature granule cells in the adult. These abnormalities are associated with a severe impairment in the acquisition of classical eyeblink conditioning, indicating cerebellar malfunction. Our data suggest that normal BDNF expression and TrkB signal transduction in the cerebellum are necessary for learning and plasticity in this model.

Original languageEnglish (US)
Pages (from-to)6990-6999
Number of pages10
JournalJournal of Neuroscience
Volume18
Issue number17
DOIs
StatePublished - Sep 1 1998
Externally publishedYes

Keywords

  • BDNF
  • Cerebellum
  • Eyeblink conditioning
  • Learning
  • Mutant mice
  • Neurotrophic factor
  • Signal transduction
  • TrkB

ASJC Scopus subject areas

  • Neuroscience(all)

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