title: Distinct muscarinic acetylcholine receptor subtypes mediate pre- and postsynaptic effects in rat neocortex.
abstract: BACKGROUND
  Cholinergic transmission has been implicated in learning, memory and cognition. However, the cellular effects induced by muscarinic acetylcholine receptors (mAChRs) activation are poorly understood in the neocortex. We investigated the effects of the cholinergic agonist carbachol (CCh) and various agonists and antagonists on neuronal activity in rat neocortical slices using intracellular (sharp microelectrode) and field potential recordings.
  
  
  RESULTS
  CCh increased neuronal firing but reduced synaptic transmission. The increase of neuronal firing was antagonized by pirenzepine (M₁/M₄ mAChRs antagonist) but not by AF-DX 116 (M₂/M₄ mAChRs antagonist). Pirenzepine reversed the depressant effect of CCh on excitatory postsynaptic potential (EPSP) but had marginal effects when applied before CCh. AF-DX 116 antagonized the depression of EPSP when applied before or during CCh. CCh also decreased the paired-pulse inhibition of field potentials and the inhibitory conductances mediated by GABA(A) and GABA(B) receptors. The depression of paired-pulse inhibition was antagonized or prevented by AF-DX 116 or atropine but only marginally by pirenzepine. The inhibitory conductances were unaltered by xanomeline (M₁/M₄ mAChRs agonist), yet the CCh-induced depression was antagonized by AF-DX 116. Linopirdine, a selective M-current blocker, mimicked the effect of CCh on neuronal firing. However, linopirdine had no effect on the amplitude of EPSP or on the paired-pulse inhibition, indicating that M-current is involved in the increase of neuronal excitability but neither in the depression of EPSP nor paired-pulse inhibition.
  
  
  CONCLUSIONS
  These data indicate that the three effects are mediated by different mAChRs, the increase in firing being mediated by M₁ mAChR, decrease of inhibition by M₂ mAChR and depression of excitatory transmission by M₄ mAChR. The depression of EPSP and increase of neuronal firing might enhance the signal-to-noise ratio, whereas the concomitant depression of inhibition would facilitate long-term potentiation. Thus, this triade of effects may represent a "neuronal correlate" of attention and learning.
authors.affiliation: Center for Anatomy, Institute for Cell Biology and Neurobiology, Charité Universitätsmedizin Berlin, Philippstr 12, 10115 Berlin, Germany.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gigout
authors.forename: Gareth A
authors.initials: GA
authors.lastname: Jones
authors.forename: Stephan
authors.initials: S
authors.lastname: Wierschke
authors.forename: Ceri H
authors.initials: CH
authors.lastname: Davies
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Watson
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Deisz
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001703:Biophysics; D018679:Cholinergic Agonists / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D019579:Neocortex / Q000166:cytology*; D009433:Neural Inhibition / Q000187:drug effects; D021122:Protein Subunits / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D018679:Cholinergic Agonists; D021122:Protein Subunits; D011976:Receptors, Muscarinic; D005680:gamma-Aminobutyric Acid