Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
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.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • Acher FC, Tellier FJ, Azerad R, Brabet IN, Fagni L, Pin JP (1997) Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes. J Med Chem 40: 3119-3129.
    • Arroyo G, Aldea M, Fuentealba J, Albillos A, Garcia AG (2003) SNX482 selectively blocks P/Q Ca2 channels and delays the inactivation of Na channels of chromaffin cells. Eur J Pharmacol 475:11-18.
    • Baccei ML, Bardoni R, Fitzgerald M (2003) Development of nociceptive synaptic inputs to the neonatal rat dorsal horn: glutamate release by capsaicin and menthol. J Physiol 549:231-242.
    • Bailey SJ, Dhillon A, Woodhall GL, Jones RS (2004) Lamina-specific differences in GABA(B) autoreceptor-mediated regulation of spontaneous GABA release in rat entorhinal cortex. Neuropharmacology 46:31- 42.
    • Berretta N, Jones RSG (1996a) A comparison of spontaneous synaptic EPSCs in layer V and layer II neurones in the rat entorhinal cortex in vitro. J Neurophysiol 76:1089 -1110.
    • Berretta N, Jones RSG (1996b) Tonic facilitation of glutamate release by presynaptic N-methyl-D-aspartate autoreceptors in the entorhinal cortex. Neuroscience 75:339 -344.
    • Billups B, Graham BP, Wong AY, Forsythe ID (2005) Unmasking group III metabotropic glutamate autoreceptor function at excitatory synapses in the rat CNS. J Physiol 565:885- 896.
    • Blackmer T, Larsen EC, Takahashi M, Martin TF, Alford S, Hamm HE (2001) G protein subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca2 -entry. Science 292:293-297.
    • Cai Z, Saugstad JA, Sorensen SD, Ciombor KJ, Zhang C, Schaffhauser H, Hubalek F, Pohl J, Duvoisin RM, Conn PJ (2001) Cyclic AMP-dependent protein kinase phosphorylates group III metabotropic glutamate receptors and inhibits their function as presynaptic receptors. J Neurochem 78:756 -766.
    • Capogna M, Gahwiler BH, Thompson SM (1995) Presynaptic enhancement of inhibitory synaptic transmission by protein kinases A and C in the rat hippocampus in vitro. J Neurosci 15:1249 -1260.
    • Casali TA, Gomez RS, Moraes-Santos T, Romano-Silva MA, Prado MA, Gomez MV (1997) Different effects of reducing agents on omega-conotoxin GVIA inhibition of [3H]-acetylcholine release from rat cortical slices and guinea-pig myenteric plexus. Br J Pharmacol 120:88 -92.
    • Chavez-Noriega LE, Stevens CF (1994) Increased transmitter release at excitatory synapses produced by direct activation of adenylate cyclase in rat hippocampal slices. J Neurosci 14:310 -317.
    • Chen C, Regehr WG (1997) The mechanism of cAMP-mediated enhancement at a cerebellar synapse. J Neurosci 17:8687- 8694.
    • De Colle C, Bessis AS, Bockaert J, Acher F, Pin JP (2000) Pharmacological characterization of the rat metabotropic glutamate receptor type 8a revealed strong similarities and slight differences with the type 4a receptor. Eur J Pharmacol 394:17-26.
    • Deitcher DL, Ueda A, Stewart BA, Burgess RW, Kidokoro Y, Schwarz TL (1998) Distinct requirements for evoked and spontaneous release of neurotransmitter are revealed by mutations in the Drosophila gene neuronal-synaptobrevin. J Neurosci 18:2028 -2039.
    • Dietrich D, Kral T, Clusmann H, Friedl M, Schramm J (2002) Presynaptic group II metabotropic glutamate receptors reduce stimulated and spontaneous transmitter release in human dentate gyrus. Neuropharmacology 42:297-305.
    • del Castillo J, Katz B (1954) Quantal components of the end-plate potential. J Physiol 124:560 -573.
    • Dobrunz LE, Stevens CF (1997) Heterogeneity of release probability, facilitation, and depletion at central synapses. Neuron 18: 995-1008.
    • Dolphin AC (2003) G-protein modulation of voltage-gated calcium channels. Pharmacol Rev 55:607- 627.
    • Evans DIP, Jones RSG, Woodhall GL (2000a) Activation of presynaptic group III metabotropic receptors enhances glutamate release in rat entorhinal cortex. J Neurophysiol 83:2519 -2525.
    • Evans DIP, Jones RSG, Woodhall GL (2000b) Activation of mGluR4 elicits a simultaneous depression of evoked, and facilitation of spontaneous EPSCs in rat entorhinal cortex in vitro. J Physiol 527P:100p.
    • Evans DIP, Jones RSG, Woodhall GL (2001) Differential actions of PKA and PKC in the regulation of glutamate release by group III mGluRs in the entorhinal cortex. J Neurophysiol 85:571-579.
    • Fabbri E, Brighenti L, Ottolenghi C (1991) Inhibition of adenylate cyclase of catfish and rat hepatocyte membranes by 9-(tetrahydro2-furyl)adenine (SQ 22536). J Enzyme Inhib 5:87-98.
    • Gasparini S, Kasyanov AM, Pietrobon D, Voronin LL, Cherubini E (2001) Presynaptic R-type calcium channels contribute to fast excitatory synaptic transmission in the rat hippocampus. J Neurosci 21:8715- 8721.
    • Gereau RW, Conn PJ (1994) Potentiation of cAMP responses by metabotropic glutamate receptors depresses excitatory synaptic transmission by a kinase-independent mechanism. Neuron 12: 1121-1129.
    • Ghirardi M, Braha O, Hochner B, Montarolo PG, Kandel ER, Dale N (1992) Roles of PKA and PKC in facilitation of evoked and spontaneous transmitter release at depressed and non-depressed synapses in Aplysia sensory neurons. Neuron 9:479 - 489.
    • Glaum SR, Miller RJ (1995) Presynaptic metabotropic glutamate receptors modulate omega-conotoxin-GVIA-insensitive calcium channels in the rat medulla. Neuropharmacology 34:953-964.
    • Goussakov IV, Fink K, Elger CE, Beck H (2000) Metaplasticity of mossy fibre synaptic transmission involves altered release probability. J Neurosci 20:3434 -3441.
    • Groemer TW, Klingauf J (2007) Synaptic vesicles recycling spontaneously and during activity belong to the same vesicle pool. Nat Neurosci 10:145-147.
    • Hell JW, Yokoyama CT, Breeze LJ, Chavkin C, Catterall WA (1995) Phosphorylation of presynaptic and postsynaptic calcium channels by cAMP-dependent protein kinase in hippocampal neurons. EMBO J 14:3036 -3044.
    • Hess G, Kuhnt U (1992) Presynaptic calcium transients evoked by paired-pulse stimulation in the hippocampal slice. Neuroreport 3:361-364.
    • Heuss C, Gerber U (2000) G-protein-independent signalling by Gprotein-coupled receptors. Trends Neurosci 23:469 - 475.
    • Heuss C, Scanziani M, Gahwiler BH, Gerber U (1999) G-proteinindependent signalling mediated by metabotropic glutamate receptors. Nat Neurosci 2:1070 -1077.
    • Hori T, Takai Y, Takahashi T (1999) Presynaptic mechanism for phorbol ester-induced synaptic potentiation. J Neurosci 19:7262-7267.
    • Hua SY, Raciborska DA, Trimble WS, Charlton MP (1998) Different VAMP/synaptobrevin complexes for spontaneous and evoked transmitter release at the crayfish neuromuscular junction. J Neurophysiol 80:3233-3246.
    • Jang IS, Jeong HJ, Katsurabayashi S, Akaike N (2002) Functional roles of presynaptic GABAA receptors on glycinergic nerve terminals in the rat spinal cord. J Physiol 541:423- 434.
    • Jarvis SE, Zamponi GW (2001) Interactions between presynaptic Ca2 channels, cytoplasmic messengers and proteins of the synaptic vesicle release complex. Trends Pharmacol Sci 22:519 -525.
    • Jones RSG, Heinemann U (1988) Synaptic and intrinsic responses of medical entorhinal cortical cells in normal and magnesium-free medium in vitro. J Neurophysiol 59:1476 -1496.
    • Jones RSG, Evans DIP, Ayman G, Woodhall GL (2004). mGlur4a Inhibits N and P/Q-type calcium channels to depress evoked glutamate release in the rat entorhinal cortex. Br Pharm Soc Abstr http://www.pa2online.org/Vol2Issue2abst021P.html.
    • Katsurabayashi S, Kubota H, Moorhouse AJ, Akaike N (2004) Differential modulation of evoked and spontaneous glycine release from rat spinal cord glycinergic terminals by the cyclic AMP/protein kinase A transduction cascade. J Neurochem 91:657- 666.
    • Katz B, Miledi R (1968) The role of calcium in neuromuscular facilitation. J Physiol 195:481- 492.
    • Kidokoro Y, Kuromi H, Delgado R, Maureira C, Oliva C, Labarca P (2004) Synaptic vesicle pools and plasticity of synaptic transmission at the Drosophila synapse. Brain Res Brain Res Rev 47(1-3):18 -32.
    • Kinoshita A, Ohishi H, Neki A, Nomura S, Shigemoto R, Takada M, Nakanishi S, Mizuno N (1996) Presynaptic localization of a metabotropic glutamate receptor, mGluR8, in the rhinencephalic areas: a light and electron microscope study in the rat. Neurosci Lett 207:61- 64.
    • Kondo S, Marty A (1997) Protein kinase A-mediated enhancement of miniature IPSC frequency by noradrenaline in rat cerebellar stellate cells. J Physiol 498:165-176.
    • Kondo S, Marty A (1998) Differential effects of noradrenaline on evoked, spontaneous and miniature IPSCs in rat cerebellar stellate cells. J Physiol 509:233-243.
    • Krieger P, Buschges A, el Manira A (1999) Calcium channels involved in synaptic transmission from reticulospinal axons in lamprey. J Neurophysiol 81:1699 -1705.
    • Levenes C, Daniel H, Crepel F (2001) Retrograde modulation of transmitter release by postsynaptic subtype 1 metabotropic glutamate receptors in the rat cerebellum. J Physiol 537:125-140.
    • Llano I, Gerschenfeld HM (1993) Beta-adrenergic enhancement of inhibitory synaptic activity in rat cerebellar stellate and Purkinje cells. J Physiol 468:201-224.
    • Llano I, Marty A (1995) Presynaptic metabotropic glutamatergic regulation of inhibitory synapses in rat cerebellar slices. J Physiol 486:163-176.
    • Lledo PM, Homburger V, Bockaert J, Vincent JD (1992) Differential G protein-mediated coupling of D2 dopamine receptors to K and Ca2 currents in rat anterior pituitary cells. Neuron 8:455- 463.
    • Llinas R, Sugimori M, Lin JW, Cherksey B (1989) Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison. Proc Natl Acad Sci U S A 86:1689 -1693.
    • McCool BA, Pin JP, Harpold MM, Brust PF, Stauderman KA, Lovinger DM (1998) Rat group I metabotropic glutamate receptors inhibit neuronal Ca2 channels via multiple signal transduction pathways in HEK 293 cells. J Neurophysiol 79:379 -391.
    • Millan C, Lujan R, Shigemoto R, Sanchez-Prieto J (2002) Subtypespecific expression of group III metabotropic glutamate receptors and Ca2 channels in single nerve terminals. J Biol Chem 277:47796 - 47803.
    • Newcomb R, Szoke B, Palma A, Wang G, Chen X, Hopkins W, Cong R, Miller J, Urge L, Tarczy-Hornoch K, Loo JA, Dooley DJ, Nadasdi L, Tsien RW, Lemos J, Miljanich G (1998) Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas. Biochemistry 37:15353-15362.
    • O'Connor V, El Far O, Bofill-Cardona E, Nanoff C, Freissmuth M, Karschin A, Airas JM, Betz H, Boehm S (1999) Calmodulin dependence of presynaptic metabotropic glutamate receptor signalling. Science 286:1180 -1184.
    • Oleskevich S, Walmsley B (2000) Phosphorylation regulates spontaneous and evoked transmitter release at a giant terminal in the rat auditory brainstem. J Physiol 526:349 -357.
    • Otis TS, Staley KJ, Mody I (1991) Perpetual inhibitory activity in mammalian brain slices generated by spontaneous GABA release. Brain Res 545:142-150.
    • Prange O, Murphy TH (1999) Correlation of miniature synaptic activity and evoked release probability in cultures of cortical neurons. J Neurosci 19:6427- 6438.
    • Qian J, Noebels JL (2001) Presynaptic Ca2 channels and neurotransmitter release at the terminal of a mouse cortical neuron. J Neurosci 21:3721-3728.
    • Reid CA, Bekkers JM, Clements JD (2003) Presynaptic Ca2 channels: a functional patchwork. Trends Neurosci 26:683- 687.
    • Rosenmund C, Stevens CF (1996) Definition of the readily releasable pool of vesicles at hippocampal synapses. Neuron 16:1197-1207.
    • Rusakov DA, Wuerz A, Kullmann DM (2004) Heterogeneity and specificity of presynaptic Ca2 current modulation by mGluRs at individual hippocampal synapses. Cereb Cortex 14:748 -758.
    • Sara Y, Virmani T, Deak F, Liu X, Kavalali ET (2005) An isolated pool of vesicles recycles at rest and drives spontaneous neurotransmission. Neuron 45:563-573.
    • Scanziani M, Capogna M, Gähwiler BH, Thompson SM (1992) Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and adenosine in the hippocampus. Neuron 9: 919 -927.
    • Scanziani M, Gahwiler BH, Thompson SM (1993) Presynaptic inhibition of excitatory synaptic transmission mediated by alpha-adrenergic receptors in area CA3 of the rat hippocampus in vitro. J Neurosci 13:5393-5401.
    • Scanziani M, Gähwiler BH, Thompson SM (1995) Presynaptic inhibition of excitatory synaptic transmission by muscarinic and metabotropic glutamate receptor activation in the hippocampus: are Ca2 channels involved? Neuropharmacology 34:1549 - 1557.
    • Schoppa NE, Westbrook GL (1997) Modulation of mEPSCs in olfactory bulb mitral cells by metabotropic glutamate receptors. J Neurophysiol 78:1468 -1475.
    • Sciancalepore M, Stratta F, Fisher ND, Cherubini E (1995) Activation of metabotropic glutamate receptors increase the frequency of spontaneous GABAergic currents through protein kinase A in neonatal rat hippocampal neurons. J Neurophysiol 74:1118 - 1122.
    • Spafford JD, Zamponi GW (2003) Functional interactions between presynaptic calcium channels and the neurotransmitter release machinery. Curr Opin Neurobiol 13:308 -314.
    • Stacey AE, Woodhall GL, Jones RSG (2002) Neurokinin-receptormediated depolarization of cortical neurons elicits an increase in glutamate release at excitatory synapses. Eur J Neurosci 16: 1896 -1906.
    • Takahashi T, Forsythe ID, Tsujimoto T, Barnes-Davies M, Onodera K (1996) Presynaptic calcium current modulation by a metabotropic glutamate receptor. Science 274:594 -597.
    • Tong G, Malenka RC, Nicoll RA (1996) Long-term potentiation in cultures of single hippocampal granule cells: a presynaptic form of plasticity. Neuron 16:1147-1157.
    • Tottene A, Moretti A, Pietrobon D (1996) Functional diversity of P-type and R-type calcium channels in rat cerebellar neurons. J Neurosci 16:6353- 6363.
    • Van der Kloot W (1991) The regulation of quantal size. Prog Neurobiol 36:93-130.
    • Vaughan CW, Connor M, Jennings EA, Marinelli S, Allen RG, Christie MJ (2001) Actions of nociceptin/orphanin FQ and other prepronociceptin products on rat rostral ventromedial medulla neurons in vitro. J Physiol 534:849 - 859.
    • Waters J, Smith SJ (2000) Phorbol esters potentiate evoked and spontaneous release by different presynaptic mechanisms. J Neurosci 20:7863-7870.
    • Wilk-Blaszczak MA, Gutowski S, Sternweis PC, Belardetti F (1994) Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells via different pertussis toxin-insensitive pathways. Neuron 12:109 -116.
    • Woodhall GL, Evans DIP, Jones RSG (2001a) Activation of presynaptic group III metabotropic glutamate receptors depresses spontaneous inhibition in layer V of the rat entorhinal cortex. Neuroscience 105:71-78.
    • Woodhall GL, Evans DIP, Cunningham MO, Jones RSG (2001b) NR2B containing NMDA auto- and heteroreceptors on entorhinal cortical neurones. J Neurophysiol 86:1644 -1651.
    • Wu LG, Saggau P (1994) Pharmacological identification of two types of presynaptic voltage dependent calcium channels at CA3-CA1 synapses of the hippocampus. J Neurosci 14:5613-5622.
    • Wu LG, Westenbroek RE, Borst JG, Catterall WA, Sakmann B (1999) Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses. J Neurosci 19:726 -736.
    • Wu LG, Borst JG, Sakmann B (1998) R-type Ca2 currents evoke transmitter release at a rat central synapse. Proc Natl Acad Sci U S A 95:4720-4725.
    • Yang J, Woodhall GL, Jones RSG (2006) Tonic facilitation of glutamate release by presynaptic NR2B-containing NMDA receptors is increased in the entorhinal cortex of chronically epileptic rats. J Neurosci 26:406 - 410.
    • Yeager RE, Yoshikami D, Rivier J, Cruz LJ, Miljanich GP (1987) Transmitter release from presynaptic terminals of electric organ: inhibition by the calcium channel antagonist omega conus toxin. J Neurosci 7:2390 -2396.
    • Zucker RS (2005) Minis: Whence and wherefore. Neuron 45: 482- 484.
    • (Accepted 4 June 2007) (Available online 16 July 2007)
  • No related research data.
  • No similar publications.

Share - Bookmark

Funded by projects

  • WT

Cite this article