title: Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors.
abstract: An anti-Hebbian form of LTP is observed at excitatory synapses made with some hippocampal interneurons. LTP induction is facilitated when postsynaptic interneurons are hyperpolarized, presumably because Ca(2+) entry through Ca(2+)-permeable glutamate receptors is enhanced. The contribution of modulatory transmitters to anti-Hebbian LTP induction remains to be established. Activation of group I metabotropic receptors (mGluRs) is required for anti-Hebbian LTP induction in interneurons with cell bodies in the CA1 stratum oriens. This region receives a strong cholinergic innervation from the septum, and muscarinic acetylcholine receptors (mAChRs) share some signaling pathways and cooperate with mGluRs in the control of neuronal excitability.We therefore examined possible interactions between group I mGluRs and mAChRs in anti-Hebbian LTP at synapses which excite oriens interneurons in rat brain slices. We found that blockade of either group I mGluRs or M1 mAChRs prevented the induction of anti-Hebbian LTP by pairing presynaptic activity with postsynaptic hyperpolarization. Blocking either receptor also suppressed long-term effects of activation of the other G-protein coupled receptor on interneuron membrane potential. However, no crossed blockade was detected for mGluR or mAchR effects on interneuron after-burst potentials or on the frequency of miniature EPSPs. Paired recordings between pyramidal neurons and oriens interneurons were obtained to determine whether LTP could be induced without concurrent stimulation of cholinergic axons. Exogenous activation of mAChRs led to LTP, with changes in EPSP amplitude distributions consistent with a presynaptic locus of expression. LTP, however, required noninvasive presynaptic and postsynaptic recordings.
  
  
  CONCLUSIONS
  In the hippocampus, a form of NMDA receptor-independent long-term potentiation (LTP) occurs at excitatory synapses made on some inhibitory neurons. This is preferentially induced when postsynaptic interneurons are hyperpolarized, depends on Ca(2+) entry through Ca(2+)-permeable AMPA receptors, and has been labeled anti-Hebbian LTP. Here we show that this form of LTP also depends on activation of both group I mGluR and M1 mAChRs. We demonstrate that these G-protein coupled receptors (GPCRs) interact, because the blockade of one receptor suppresses long-term effects of activation of the other GPCR on both LTP and interneuron membrane potential. This LTP was also detected in paired recordings, although only when both presynaptic and postsynaptic recordings did not perturb the intracellular medium. Changes in EPSP amplitude distributions in dual recordings were consistent with a presynaptic locus of expression.
authors.affiliation: Inserm U1127, CNRS UMR7225, Sorbonne Universités, UPMC UMR S1127, Institut du Cerveau et de la Moelle épinière, Paris 75013, France, and Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom caroline.leduigou@gmail.com.
authors.forename: Caroline
authors.identifier: http://orcid.org/0000-0003-4963-4947
authors.initials: C
authors.lastname: Le Duigou
authors.affiliation: Inserm U1127, CNRS UMR7225, Sorbonne Universités, UPMC UMR S1127, Institut du Cerveau et de la Moelle épinière, Paris 75013, France, and.
authors.forename: Etienne
authors.identifier: http://orcid.org/0000-0003-3287-3845
authors.initials: E
authors.lastname: Savary
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom.
authors.forename: Dimitri M
authors.initials: DM
authors.lastname: Kullmann
authors.affiliation: Inserm U1127, CNRS UMR7225, Sorbonne Universités, UPMC UMR S1127, Institut du Cerveau et de la Moelle épinière, Paris 75013, France, and.
authors.forename: Richard
authors.initials: R
authors.lastname: Miles
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009415:Nerve Net / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D018678:Cholinergic Agents; D018683:Excitatory Amino Acid Agents; D043643:Receptor, Muscarinic M1; D018094:Receptors, Metabotropic Glutamate; D026941:Sodium Channel Blockers; C104077:metabotropic glutamate receptor type 1; D013779:Tetrodotoxin; D002118:Calcium
keywords: LTP; hippocampus; interneuron; metabotropic glutamate receptors; muscarinic receptors