@article {Perez-Rosello9259, author = {Tamara Perez-Rosello and Charles T. Anderson and Francisco J. Schopfer and Yanjun Zhao and David Gilad and Sonia R. Salvatore and Bruce A. Freeman and Michal Hershfinkel and Elias Aizenman and Thanos Tzounopoulos}, title = {Synaptic Zn2+ Inhibits Neurotransmitter Release by Promoting Endocannabinoid Synthesis}, volume = {33}, number = {22}, pages = {9259--9272}, year = {2013}, doi = {10.1523/JNEUROSCI.0237-13.2013}, publisher = {Society for Neuroscience}, abstract = {Although it is well established that many glutamatergic neurons sequester Zn2+ within their synaptic vesicles, the physiological significance of synaptic Zn2+ remains poorly understood. In experiments performed in a Zn2+-enriched auditory brainstem nucleus{\textemdash}the dorsal cochlear nucleus{\textemdash}we discovered that synaptic Zn2+ and GPR39, a putative metabotropic Zn2+-sensing receptor (mZnR), are necessary for triggering the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). The postsynaptic production of 2-AG, in turn, inhibits presynaptic probability of neurotransmitter release, thus shaping synaptic strength and short-term synaptic plasticity. Zn2+-induced inhibition of transmitter release is absent in mutant mice that lack either vesicular Zn2+ or the mZnR. Moreover, mass spectrometry measurements of 2-AG levels reveal that Zn2+-mediated initiation of 2-AG synthesis is absent in mice lacking the mZnR. We reveal a previously unknown action of synaptic Zn2+: synaptic Zn2+ inhibits glutamate release by promoting 2-AG synthesis.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/33/22/9259}, eprint = {https://www.jneurosci.org/content/33/22/9259.full.pdf}, journal = {Journal of Neuroscience} }