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

Similar Intracellular Ca2+Requirements for Inactivation and Facilitation of Voltage-Gated Ca2+Channels in a Glutamatergic Mammalian Nerve Terminal

“…1D) (Takahashi et al, 1996;Kushmerick et al, 2004). Metabotropic GluRs have been localized synaptically and extrasynaptically in the calyx terminal (Elezgarai et al, 1999(Elezgarai et al, , 2001.…”

“…Since presynaptic depolarization can trigger the release of large amounts of glutamate from the calyx, we had to consider a negative regulation of I Ca(V) by activation of mGluRs (Takahashi et al, 1996) or via retroinhibition by cannabinoids acting on CB1Rs (Kushmerick et al, 2004). Additionally or alternatively, a decrease in I Ca(V) amplitude could be caused by depletion of Ca 2ϩ ions from the synaptic cleft because of concomitant activation of postsynaptic Ca 2ϩ -permeable GluR channels (Borst and Sakmann, 1999).…”

Coincident Activation of Metabotropic Glutamate Receptors and NMDA Receptors (NMDARs) Downregulates Perisynaptic/Extrasynaptic NMDARs and Enhances High-Fidelity Neurotransmission at the Developing Calyx of Held Synapse

“…4 B, C). It has been shown that group I mGluRs are expressed in MNTB neurons and regulate transmitter release through presynaptic CB1 cannabinoid receptors (CB1Rs) (Kushmerick et al, 2004). To test whether downregulation of summated NMDAR-EPSCs involves CB1Rs, we applied the CB1R antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251; 5 M) before and during the induction paradigm.…”

Control of neuronal excitability by Group I metabotropic glutamate receptors

“…For example, U73122 inhibits the phospholipase C and there are selective inhibitors for protein kinases PKA, PKC, and PKG, among others (Brager and Jonston 2007;Ji et al 2012;Li et al 2016;Nugent et al 2009;Sekizawa et al 2006;Shen and Johnson 2013;Shim et al 2016). Finally, Ca 2+ -dependent signaling can be blocked by intracellular application of strong Ca 2+ buffering, such as millimolar BAPTA (Kushmerick et al 2004;Li et al 2016;Sekizawa and Bonham et al 2006). The use of these drugs has permitted the characterization of Group I signaling pathways (see below).…”

“…Their activation can trigger release of endocannabinoides that feed back onto the nerve terminal, inhibiting the presynaptic Ca 2+ transient and neurotransmitter release, a form of presynaptic short-term plasticity (Kreitzer and Regehr 2001;Kushmerick et al 2004;Maejima et al 2001;Morishita et al 1998;Ohno-Shosaku et al 2002;Varma et al 2001;Yoshida et al 2002). Group I mGlu receptors are also involved in the generation of long-term synaptic plasticity, often in partnership with pre-synaptic CB1 receptors (Chevaleyre and Castillo 2004;Edwards et al 2006;Gladding et al 2009;Kano and Wantanabe 2017;Olmo et al 2016).…”