Presynaptic M3 muscarinic cholinoceptors mediate inhibition of excitatory synaptic transmission in area CA1 of rat hippocampus.
Acetylcholine can modulate hippocampal network function through activation of both nicotinic and muscarinic acetylcholine receptors (mAChRs). All five mAChR subtypes have been identified in the hippocampus. Besides by their involvement in excitability of hippocampal cells, synaptic plasticity and memory, a large body of research has demonstrated the involvement of presynaptic mAChRs in the inhibition of glutamatergic transmission in the hippocampus. Over the years, however, pharmacological and molecular genetic studies have yielded quite contradictory results regarding the mAChR subtype(s) involved. In this study, multi-electrode array technology was used for the pharmacological elucidation of the subtype of mAChR mediating the depression of excitatory synaptic transmission at the SC-CA1 synapse. Using selective antagonists (VU0255035, MT7, tripinamide, MT3) and allosteric potentiators (VU 10010, VU 0238429) the involvement of M1, M2, M4, and M5 subtypes was ruled out thereby implying a major modulatory role for M3 receptors in the inhibition of excitatory synaptic transmission in area CA1 of rat hippocampus.
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Filip
F
de Vin
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Sze Men
SM
Choi
Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
Maria L
ML
Bolognesi
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium. Electronic address: Romain.Lefebvre@UGent.be.
Romain A
RA
Lefebvre
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3
Glutamatergic neurotransmission; Hippocampal CA1; Presynaptic mACh receptors; fEPSP