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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Publisher: Elsevier Science
Journal: Neuroscience
Languages: English
Types: Article
Subjects: AgTx, agatoxin IVA, VGCC, voltage-gated calcium channel, AC, adenylyl cyclase, entorhinal cortex, mGluR, metabotropic glutamate receptor, mEPSC, miniature excitatory postsynaptic current, sEPSC, spontaneous excitatory postsynaptic current, glutamate release, TTX, tetrodotoxin, RRP, readily releasable pool, CPPG, (RS)-cyclopropyl-4-phosphonophenylglycine, eEPSC, evoked excitatory postsynaptic current, SNx, SNX-482, Behavioural Neuroscience, presynaptic metabotropic receptors, NMDA, N-methyl-d-aspartate, AP, action potential, ACPT-1 (1S, 3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid, CTx, ω-conotoxin GVIA, ACSF, artificial cerebrospinal fluid, KS, Kolmogorov-Smirnoff, SQ22536, 9-tetrahydro-2-furanyl)-9H-purin-6-amine, EC, entorhinal cortex, mIPSC, miniature inhibitory postsynaptic current, IEI, inter-event interval, PKA, protein kinase A
Neurotransmitter release at CNS synapses occurs via both action potential-dependent and independent mechanisms, and it has generally been accepted that these two forms of release are regulated in parallel. We examined the effects of activation of group III metabotropic glutamate receptors (mGluRs) on stimulus-evoked and spontaneous glutamate release onto entorhinal cortical neurones in rats, and found a differential regulation of action potential-dependent and independent forms of release. Activation of presynaptic mGluRs depressed the amplitude of stimulus-evoked excitatory postsynaptic currents, but concurrently enhanced the frequency of spontaneous excitatory currents. Moreover, these differential effects on glutamate release were mediated by pharmacologically separable mechanisms. Application of the specific activator of adenylyl cyclase, forskolin, mimicked the effect of mGluR activation on spontaneous, but not evoked release, and inhibition of adenylyl cyclase with 9-tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) blocked mGluR-mediated enhancement of spontaneous release, but not depression of evoked release. Occlusion studies with calcium channel blockers suggested that the group III mGluRs might depress evoked release through inhibition of both N and P/Q, but not R-type calcium channels. We suggest that the concurrent depression of action potential-evoked, and enhancement of action potential-independent glutamate release operate through discrete second messenger/effector systems at excitatory entorhinal terminals in rat brain. © 2007 IBRO.
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    • (Accepted 4 June 2007) (Available online 16 July 2007)
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