RT Journal Article
SR Electronic
T1 Simultaneous Monitoring of Presynaptic Transmitter Release and Postsynaptic Receptor Trafficking Reveals an Enhancement of Presynaptic Activity in Metabotropic Glutamate Receptor-Mediated Long-Term Depression
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5867
OP 5877
DO 10.1523/JNEUROSCI.1508-12.2013
VO 33
IS 13
A1 Wei Xu
A1 Yiu Chung Tse
A1 Frederick A. Dobie
A1 Michel Baudry
A1 Ann Marie Craig
A1 Tak Pan Wong
A1 Yu Tian Wang
YR 2013
UL http://www.jneurosci.org/content/33/13/5867.abstract
AB Although the contribution of postsynaptic mechanisms to long-term synaptic plasticity has been studied extensively, understanding the contribution of presynaptic modifications to this process lags behind, primarily because of a lack of techniques with which to directly and quantifiably measure neurotransmitter release from synaptic terminals. Here, we developed a method to measure presynaptic activity through the biotinylation of vesicular transporters in vesicles fused with presynaptic membranes during neurotransmitter release. This method allowed us for the first time to selectively quantify the spontaneous or evoked release of glutamate or GABA at their respective synapses. Using this method to investigate presynaptic changes during the expression of group I metabotropic glutamate receptor (mGluR1/5)-mediated long-term depression (LTD) in cultured rat hippocampal neurons, we discovered that this form of LTD was associated with increased presynaptic release of glutamate, despite reduced miniature EPSCs measured with whole-cell recording. Moreover, we found that specific blockade of AMPA receptor (AMPAR) endocytosis with a membrane-permeable GluR2-derived peptide not only prevented the expression of LTD but also eliminated LTD-associated increase in presynaptic release. Thus, our work not only demonstrates that mGluR1/5-mediated LTD is associated with increased endocytosis of postsynaptic AMPARs but also reveals an unexpected homeostatic/compensatory increase in presynaptic release. In addition, this study indicates that biotinylation of vesicular transporters in live cultured neurons is a valuable tool for studying presynaptic function.