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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Woodhall, G.L.; Ayman, G.; Jones, R.S.G. (2007)
Publisher: Elsevier Science
Journal: Neuroscience
Languages: English
Types: Article
Subjects: Neuroscience(all), entorhinal cortex, Behavioural Neuroscience, SQ22536, 9-tetrahydro-2-furanyl)-9H-purin-6-amine, glutamate release, sEPSC, spontaneous excitatory postsynaptic current, CPPG, (RS)-cyclopropyl-4-phosphonophenylglycine, PKA, protein kinase A, mIPSC, miniature inhibitory postsynaptic current, NMDA, N-methyl-d-aspartate, AP, action potential, KS, Kolmogorov-Smirnoff, TTX, tetrodotoxin, EC, entorhinal cortex, ACPT-1 (1S, 3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid, ACSF, artificial cerebrospinal fluid, presynaptic metabotropic receptors, RRP, readily releasable pool, mEPSC, miniature excitatory postsynaptic current, AgTx, agatoxin IVA, IEI, inter-event interval, VGCC, voltage-gated calcium channel, CTx, ω-conotoxin GVIA, SNx, SNX-482, eEPSC, evoked excitatory postsynaptic current, mGluR, metabotropic glutamate receptor, AC, adenylyl cyclase
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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