Activation of Group II Metabotropic Glutamate Receptors Inhibits Glutamatergic Transmission in the Rat Entorhinal Cortex via Reduction of Glutamate Release Probability

Abstract

Glutamate interacts with ionotropic and metabotropic glutamate receptors (mGluRs). Whereas the entorhinal cortex (EC) is a principal structure involved in learning and memory, the roles of mGluRs in synaptic transmission in the EC have not been completely determined. Here, we show that activation of group II mGluRs (mGluR II) induced robust depression of glutamatergic transmission in the EC. The mGluR II--induced depression was due to a selective reduction of presynaptic release probability without alterations of the quantal size and the number of release sites. The mechanisms underlying mGluR II--mediated suppression of glutamate release included the inhibition of presynaptic release machinery and the depression of presynaptic P/Q-type Ca 21 channels. Whereas mGluR II--induced depression required the function of Ga i/o proteins, protein kinase A (PKA) pathway was only involved in mGluR II--mediated inhibition of release machinery and thereby partially required for mGluR II--induced inhibition of glutamate release. Presynaptic stimulation at 5 Hz for 10 min also induced depression of glutamatergic transmission via activation of presynaptic mGluR II suggesting an endogenous role for mGluR II in modulating glutamatergic transmission.

mGluR2/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both presynaptic and postsynaptic actions

“…Apparent species differences in mGluR2/3 signaling in primates vs rodents Previous physiological and biochemical studies in rodent PFC have found that mGluR2/3 stimulation reduces glutamate release and decreases excitation of the postsynaptic neuron. 23,27,61,62 Although these findings are consistent with our high-dose APDC data, they are at odds with our findings that low doses of mGluR2/3 agonists increase neuronal firing. There are several possible explanations for the discrepancy between the rodent literature and the current data from primates.…”

“…This reduction in firing with higher doses is likely due to drug actions at receptors on the glutamatergic axon and/or perisynaptic astrocytes, where mGluR2/3 stimulation reduces glutamate release [61][62][63] and increases glutamate uptake, 28 respectively. These effects appear to be less responsive to drug than the potent, postsynaptic actions.…”

Neurotensinergic augmentation of glutamate release at the perforant path-granule cell synapse in rat dentate gyrus: Roles of L-Type Ca2+ channels, calmodulin and myosin light-chain kinase

“…Cells in the slices were visually identified with infrared video microscopy and differential interference contrast optics (Ramanathan et al, 2012; Wang et al, 2012; Wang et al, 2013). Recording electrodes were filled with the solution containing (in mM) 100 Cs-gluconate, 0.6 EGTA, 5 MgCl 2 , 8 NaCl, 2 ATP 2 Na, 0.3 GTPNa, 40 HEPES and 1 QX-314 (pH 7.3).…”

Vasopressin facilitates GABAergic transmission in rat hippocampus via activation of V1A receptors

“…As described previously (Deng and Lei, 2008; Deng et al, 2006; Wang et al, 2012; Wang et al, 2011; Xiao et al, 2009b), the recording electrodes were filled with (mM) 100 cesium gluconate, 0.6 EGTA, 5 MgCl 2 , 8 NaCl, 2 ATP 2 Na, 0.3 GTPNa, 40 HEPES, and 1 QX-314 (pH 7.3). The extracellular solution comprised (mM) 130 NaCl, 24 NaHCO 3 , 3.5 KCl, 1.25 NaH 2 PO 4 , 1.5 MgCl 2 , 2.5 CaCl 2 and 10 glucose, saturated with 95% O 2 and 5% CO 2 (pH 7.4).…”