title: Metabotropic glutamate receptor 8-expressing nerve terminals target subsets of GABAergic neurons in the hippocampus.
abstract: Presynaptic metabotropic glutamate receptors (mGluRs) show a highly selective expression and subcellular location in nerve terminals modulating neurotransmitter release. We have demonstrated that alternatively spliced variants of mGluR8, mGluR8a and mGluR8b, have an overlapping distribution in the hippocampus, and besides perforant path terminals, they are expressed in the presynaptic active zone of boutons making synapses selectively with several types of GABAergic interneurons, primarily in the stratum oriens. Boutons labeled for mGluR8 formed either type I or type II synapses, and the latter were GABAergic. Some mGluR8-positive boutons also expressed mGluR7 or vasoactive intestinal polypeptide. Interneurons strongly immunopositive for the muscarinic M2 or the mGlu1 receptors were the primary targets of mGluR8-containing terminals in the stratum oriens, but only neurochemically distinct subsets were innervated by mGluR8-enriched terminals. The majority of M2-positive neurons were mGluR8 innervated, but a minority, which expresses somatostatin, was not. Rare neurons coexpressing calretinin and M2 were consistently targeted by mGluR8-positive boutons. In vivo recording and labeling of an mGluR8-decorated and strongly M2-positive interneuron revealed a trilaminar cell with complex spike bursts during theta oscillations and strong discharge during sharp wave/ripple events. The trilaminar cell had a large projection from the CA1 area to the subiculum and a preferential innervation of interneurons in the CA1 area in addition to pyramidal cell somata and dendrites. The postsynaptic interneuron type-specific expression of the high-efficacy presynaptic mGluR8 in both putative glutamatergic and in identified GABAergic terminals predicts a role in adjusting the activity of interneurons depending on the level of network activity.
authors.affiliation: Department of Pharmacology, Oxford University, Oxford OX1 3TH, United Kingdom. francesco.ferraguti@uibk.ac.at
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraguti
authors.forename: Thomas
authors.initials: T
authors.lastname: Klausberger
authors.forename: Philip
authors.initials: P
authors.lastname: Cobden
authors.forename: Agnes
authors.initials: A
authors.lastname: Baude
authors.forename: J David B
authors.initials: JD
authors.lastname: Roberts
authors.forename: Peter
authors.initials: P
authors.lastname: Szucs
authors.forename: Ayae
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.forename: Peter
authors.initials: P
authors.lastname: Somogyi
authors.forename: Yannis
authors.initials: Y
authors.lastname: Dalezios
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D064032:Calbindin 2; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003952:Diagnostic Imaging / Q000379:methods; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007395:Interneurons / Q000378:metabolism / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013569:Synapses / Q000145:classification / Q000378:metabolism / Q000648:ultrastructure; D014162:Transfection / Q000379:methods; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C576512:Calb2 protein, rat; D064032:Calbindin 2; D010320:Parvalbumins; D011498:Protein Precursors; D043585:Receptor, Muscarinic M2; D018094:Receptors, Metabotropic Glutamate; D064030:S100 Calcium Binding Protein G; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C111435:metabotropic glutamate receptor 8; D014660:Vasoactive Intestinal Peptide; D005680:gamma-Aminobutyric Acid; C060249:procholecystokinin; D002766:Cholecystokinin; D005968:Glutamate Decarboxylase