title: NMDA and AMPA receptors contribute to the nicotinic cholinergic excitation of CA1 interneurons in the rat hippocampus.
abstract: In the hippocampus, glutamatergic inputs to pyramidal neurons and interneurons are modulated by alpha7* and alpha3beta4* nicotinic acetylcholine receptors (nAChRs), respectively, present in glutamatergic neurons. This study examines how nicotinic AMPA, and NMDA receptor nAChR activities are integrated to regulate the excitability of CA1 stratum radiatum (SR) interneurons in rat hippocampal slices. At resting membrane potentials and in the presence of extracellular Mg2+ (1 mM), nicotinic agonists triggered in SR interneurons excitatory postsynaptic currents (EPSCs) that had two components: one mediated by AMPA receptors, and the other by NMDA receptors. As previously shown, nicotinic agonist-triggered EPSCs resulted from glutamate released by activation of alpha3beta4* nAChRs in glutamatergic neurons/fibers synapsing directly onto the neurons under study. The finding that CNQX caused more inhibition of nicotinic agonist-triggered EPSCs than expected from the blockade of postsynaptic AMPA receptors indicated that this nicotinic response also depended on the AMPA receptor activity in the glutamatergic neurons synapsing onto the interneuron under study. Nicotinic agonists always triggered action potentials in CA1 SR interneurons. In most interneurons, these action potentials resulted from activation of somatodendritic AMPA receptors and alpha7* nAChRs. In interneurons expressing somatodendritic alpha4beta2* nAChRs, activation of these receptors caused sufficient membrane depolarization to remove the Mg2+-induced block of somatodendritic NMDA receptors; in these neurons, nicotinic agonist-triggered action potentials were partially dependent on NMDA receptor activation. Removing extracellular Mg2+ or clamping the neuron at positive membrane potentials revealed the existence of a tonic NMDA current in SR interneurons that was unaffected by nAChR activation or inhibition. Thus integration of the activities of nAChRs, NMDA, and AMPA receptors in different compartments of CA1 neurons contributes to the excitability of CA1 SR interneurons.
authors.affiliation: Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Manickavasagom
authors.initials: M
authors.lastname: Alkondon
authors.forename: Edna F R
authors.initials: EF
authors.lastname: Pereira
authors.forename: Edson X
authors.initials: EX
authors.lastname: Albuquerque
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic