title: Bidirectional modulation of long-term potentiation by carbachol via M1 and M2 muscarinic receptors in guinea pig hippocampal mossy fiber-CA3 synapses.
abstract: Participation of muscarinic M1 and M2 receptors in the modulation of long-term potentiation (LTP) was studied in the mossy fiber-CA3 synapse of guinea pig hippocampal slices. The magnitude of tetanus-induced LTP was attenuated in the presence of 0.01-0.1 microM carbachol, at which concentration the pre-tetanus amplitude of field excitatory postsynaptic potential (fEPSP) was not affected. The attenuation of LTP by the low concentration of carbachol was reversed by an M2 muscarinic antagonist, AF-DX 116, but not by an M1 antagonist, pirenzepine. On the contrary, a high concentration (10 microM) of carbachol decreased the pre-tetanic amplitude of fEPSP, however, the magnitude of LTP was significantly larger than that in control slices in which pre-tetanic amplitude of fEPSP was reduced to the level of carbachol-treated slices by reducing the intensity of stimulation or extracellular Ca2+ concentration. The augmentation of LTP by 10 microM carbachol was blocked by pirenzepine but not by AF-DX 116. These results suggest that the synaptic plasticity in the guinea pig hippocampal mossy fiber-CA3 synapse is inhibited and facilitated by muscarinic agonist through muscarinic M2 and M1 receptors to inhibit and facilitate the LTP, respectively.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.forename: M
authors.initials: M
authors.lastname: Satoh
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D015763:2-Amino-5-phosphonovalerate; D002217:Carbachol; C048593:otenzepad