Retroinhibition of Presynaptic Ca2+Currents by Endocannabinoids Released via Postsynaptic mGluR Activation at a Calyx Synapse

• DOI: 10.1523/jneurosci.0768-04.2004
• Publication Date: 2004-06-30T16:23:28Z
• Authors: Christopher Kushm...; Gareth D. Price; Holger Taschenberger; Nagore Puente; Robert Renden; Jacques I. Wadiche; Robert M. Duvoisin; Pedro Grandes; Henrique von Gers...
• Keywords: AM251

We investigated the mechanisms by which activation of group I metabotropic glutamate receptors (mGluRs) and CB1 cannabinoid (CB1Rs) leads to inhibition synaptic currents at calyx Held synapse in medial nucleus trapezoid body (MNTB) rat auditory brainstem. In ∼50% MNTB neurons tested, mGluRs specific agonist (s)-3,5-dihydroxyphenylglycine (DHPG) reversibly inhibited AMPA receptor- NMDA receptor-mediated EPSCs a similar extent reduced paired-pulse depression, suggestive an release. Presynaptic voltage-clamp experiments revealed reversible reduction Ca 2+ DHPG, with no significant modification presynaptic action potential waveform. Likewise, tested cells, receptor ( R )-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN) EPSCs, currents, exocytosis. For given cell, amount DHPG correlated that WIN. Moreover, inhibitory was blocked CB1R antagonist N -(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) occluded WIN, indicating WIN operate via common pathway. The but not abolished after dialyzing 40 m BAPTA into postsynaptic suggesting activated mGluRs. Light electron microscopy immunolabeling indicated expression CB1Rs localization mGluR1a. Our data suggest triggers -dependent release endocannabinoids activate on terminal, current