title: Synergistic interactions between kainate and mGlu receptors regulate bouton Ca signalling and mossy fibre LTP.
abstract: It is currently unknown why glutamatergic presynaptic terminals express multiple types of glutamate receptors. We have addressed this question by studying both acute and long-term regulation of mossy fibre function in the hippocampus. We find that inhibition of both mGlu₁ and mGlu₅ receptors together can block the induction of mossy fibre LTP. Furthermore, mossy fibre LTP can be induced by the pharmacological activation of either mGlu₁ or mGlu₅ receptors, provided that kainate receptors are also stimulated. Like conventional mossy fibre LTP, chemically-induced mossy fibre LTP (chem-LTPm) depends on Ca²⁺ release from intracellular stores and the activation of PKA. Similar synergistic interactions between mGlu receptors and kainate receptors were observed at the level of Ca²⁺ signalling in individual giant mossy fibre boutons. Thus three distinct glutamate receptors interact, in both an AND and OR gate fashion, to regulate both immediate and long-term presynaptic function in the brain.
authors.affiliation: MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
authors.forename: Sheila L
authors.initials: SL
authors.lastname: Dargan
authors.forename: Mascia
authors.initials: M
authors.lastname: Amici
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: Zuner A
authors.initials: ZA
authors.lastname: Bortolotto
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D017774:Long-Term Potentiation; D019599:Mossy Fibers, Hippocampal / Q000201:enzymology / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate