title: Cholinergic suppression of excitatory synaptic transmission in layers II/III of the parasubiculum.
abstract: Layer II of the parasubiculum (PaS) receives excitatory synaptic input from the CA1 region of the hippocampus and sends a major output to layer II of the medial and lateral entorhinal cortex. The PaS also receives heavy cholinergic innervation from the medial septum, which contributes to the generation of theta-frequency (4-12 Hz) electroencephalographic (EEG) activity. Cholinergic receptor activation exerts a wide range of effects in other areas of the hippocampal formation, including membrane depolarization, changes in neuronal excitability, and suppression of excitatory synaptic responses. The present study was aimed at determining how cholinergic receptor activation modulates excitatory synaptic input to the layer II/III neurons of the PaS in acute brain slices. Field excitatory postsynaptic potentials (fEPSPs) in layer II/III of the PaS were evoked by stimulation of either layer I afferents, or ascending inputs from layer V. Bath-application of the cholinergic agonist carbachol (0.5-10 μM) suppressed the amplitude of fEPSPs evoked by both superficial- and deep layer stimulation, and also enhanced paired-pulse facilitation. Constant bath-application of the GABA(A) antagonist bicuculline (10 μM) failed to eliminate the suppression, indicating that the cholinergic suppression of fEPSPs is not due to increased inhibitory tone. The muscarinic receptor antagonist atropine (1 μM) blocked the suppression of fEPSPs, and the selective M(1)-preferring receptor antagonist pirenzepine (1 μM), but not the M(2)-preferring antagonist methoctramine (1-5 μM), also significantly attenuated the suppression. Therefore, cholinergic receptor activation suppresses excitatory synaptic input to layer II/III neurons of the PaS, and this suppression is mediated in part by M(1) receptor activation.
authors.affiliation: Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, QC, Canada H4B 1R6.
authors.forename: S D
authors.initials: SD
authors.lastname: Glasgow
authors.forename: I
authors.initials: I
authors.lastname: Glovaci
authors.forename: L S
authors.initials: LS
authors.lastname: Karpowicz
authors.forename: C A
authors.initials: CA
authors.lastname: Chapman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D018678:Cholinergic Agents; D058787:GABA-A Receptor Antagonists; D002217:Carbachol; D001640:Bicuculline