BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses.

Abstract

Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines - a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity.

• Authors: William J Tyler, Xiao-lei Zhang, Kenichi Hartman, Jochen Winterer, Wolfgang Muller, Patric K Stanton, Lucas Pozzo-Miller
• Journal: The Journal of physiology (J Physiol) Vol. 574 Issue Pt 3 Pg. 787-803 (Aug 01 2006) ISSN: 0022-3751 [Print] England
• PMID: 16709633 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor

Topics

• Animals
• Animals, Newborn
• Brain-Derived Neurotrophic Factor (pharmacology)
• Cells, Cultured
• Computer Simulation
• Excitatory Postsynaptic Potentials (drug effects, physiology)
• Hippocampus (drug effects, physiology)
• Models, Neurological
• Models, Statistical
• Rats
• Rats, Sprague-Dawley
• Synaptic Transmission (drug effects, physiology)
• Synaptic Vesicles (drug effects, physiology)