Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure

Alexandre R. Carter, Chinfei Chen, Phillip M. Schwartz, Rosalind A. Segal

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

Neurotrophins are key regulators of neuronal survival and function. Here we show that TrkB, the receptor for brain-derived neurotrophic factor (BDNF), is located at parallel fiber to Purkinje cell (PF/PC) synapses of the cerebellum. To determine the effects of TrkB receptor activation on synapse formation and function, we examined the parallel fiber to Purkinje cell synapses of mice with a targeted deletion of the BDNF gene. Although Purkinje cell dendrites are abnormal in BDNF -/- mice, PF/PC synapses are still able to form. Immunohistochemical analysis of mutant animals revealed the formation of numerous PF/PC synapses with the appropriate apposition of presynaptic and postsynaptic proteins. These synapses are functional, and no differences were detected in the waveform of evoked EPSCs, the amplitude of spontaneous mini-EPSCs, or the response to prolonged 10 Hz stimulus trains. However, paired-pulse facilitation, a form of short-term plasticity, is significantly decreased in BDNF -/- mice. Detailed ultrastructural analysis of the presynaptic terminals demonstrated that this change in synaptic function is accompanied by an increase in the total number of synaptic vesicles in mutant mice and a decrease in the proportion of vesicles that are docked. These data suggest that BDNF regulates both the mechanisms that underlie short-term synaptic plasticity and the steady-state relationship between different vesicle pools within the terminal.

Original languageEnglish
Pages (from-to)1316-1327
Number of pages12
JournalJournal of Neuroscience
Volume22
Issue number4
DOIs
StatePublished - Feb 15 2002

Keywords

  • BDNF
  • Cerebellum
  • Facilitation
  • Neurotrophin
  • Presynaptic plasticity
  • Trk receptor
  • Ultrastructure

Fingerprint Dive into the research topics of 'Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure'. Together they form a unique fingerprint.

Cite this