@article {Zhang10270, author = {Xiao-lei Zhang and Zhen-yu Zhou and Jochen Winterer and Wolfgang M{\"u}ller and Patric K. Stanton}, title = {NMDA-Dependent, But Not Group I Metabotropic Glutamate Receptor-Dependent, Long-Term Depression at Schaffer Collateral{\textendash}CA1 Synapses Is Associated with Long-Term Reduction of Release from the Rapidly Recycling Presynaptic Vesicle Pool}, volume = {26}, number = {40}, pages = {10270--10280}, year = {2006}, doi = {10.1523/JNEUROSCI.3091-06.2006}, publisher = {Society for Neuroscience}, abstract = {Postsynaptic alterations have been suggested to account for NMDA receptor (NMDAR)-dependent long-term depression (LTD) and long-term potentiation of synaptic strength, although there is substantial evidence supporting changes in presynaptic release. Direct chemical activation of either NMDA or group I metabotropic glutamate receptor (mGluR1) elicits LTD of similar magnitudes, but it is unknown whether they share common expression mechanisms. Using dual-photon laser-scanning microscopy of FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide] to directly visualize presynaptic vesicular release from the rapidly recycling vesicle pool (RRP) at Schaffer collateral terminals in field CA1 of rat hippocampal slices, we found that a persistent reduction in vesicular release from the RRP is induced by NMDA-LTD but not by mGluR1-LTD. Variance-mean analyses of Schaffer collateral release probability (Pr) at varying extracellular calcium concentrations confirmed that NMDA-LTD was associated with reduced Pr, whereas mGluR1-LTD was not. Pharmacological isolation of NMDAR-dependent and mGluR-dependent forms of stimulus-evoked LTD revealed that both are composed of a combination of presynaptic and postsynaptic alterations. However, when group I mGluR-dependent LTD was isolated by combining an NMDAR blocker with a group II mGluR antagonist, this form of LTD was purely postsynaptic. The nitric oxide synthase inhibitor Nω-nitro-l-arginine blocked the induction of NMDA-LTD but did not alter mGluR-LTD, consistent with a selective role for nitric oxide as a retrograde messenger mediating NMDA-LTD. These data demonstrate that single synapses can express multiple forms of LTD with different sites of expression, that NMDA-LTD is a combination of presynaptic and postsynaptic alterations, but that group I mGluR-LTD appears to be expressed entirely postsynaptically.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/26/40/10270}, eprint = {https://www.jneurosci.org/content/26/40/10270.full.pdf}, journal = {Journal of Neuroscience} }