Reduced presynaptic efficiency of excitatory synaptic transmission impairs LTP in the visual cortex of BDNF-heterozygous mice

Eur J Neurosci. 2006 Dec;24(12):3519-31. doi: 10.1111/j.1460-9568.2006.05242.x.


The neurotrophin brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival, axonal and dendritic growth and synapse formation. BDNF has also been reported to mediate visual cortex plasticity. Here we studied the cellular mechanisms of BDNF-mediated changes in synaptic plasticity, excitatory synaptic transmission and long-term potentiation (LTP) in the visual cortex of heterozygous BDNF-knockout mice (BDNF(+/-)). Patch-clamp recordings in slices showed an approximately 50% reduction in the frequency of miniature excitatory postsynaptic currents (mEPSCs) compared to wild-type animals, in the absence of changes in mEPSC amplitudes. A presynaptic impairment of excitatory synapses from BDNF(+/-) mice was further indicated by decreased paired-pulse ratio and faster synaptic fatigue upon prolonged repetitive stimulation at 40 Hz. In accordance, presynaptic theta-burst stimulation (TBS) failed to induce LTP at layer IV to layers II-III synapses during extracellular field-potential recordings in BDNF(+/-) animals. Changes in postsynaptic function could not be detected, as no changes were observed in either the amplitudes of evoked EPSCs, the ratios of AMPA : NMDA currents or the kinetics of evoked AMPA and NMDA EPSCs. In line with this observation, an LTP pairing paradigm that relies on direct postsynaptic depolarization under patch-clamp conditions could be induced successfully in BDNF(+/-) animals. These data suggest that a chronic reduction in the expression of BDNF to nearly 50% attenuates the efficiency of presynaptic glutamate release in response to repetitive stimulation, thereby impairing presynaptically evoked LTP in the visual cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / deficiency
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Calcium / pharmacology
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Long-Term Potentiation / radiation effects
  • Mice
  • Mice, Knockout
  • N-Methylaspartate / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Patch-Clamp Techniques / methods
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Presynaptic Terminals / radiation effects
  • Quinoxalines / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptic Transmission / radiation effects
  • Time Factors
  • Visual Cortex / cytology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Brain-Derived Neurotrophic Factor
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Quinoxalines
  • FG 9041
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Calcium