title: Acetylcholine Facilitates a Depolarization-Induced Enhancement of Inhibition in Rat CA1 Pyramidal Neurons.
abstract: Cholinergic mechanisms in the hippocampus regulate forms of synaptic plasticity linked with cognition and spatial navigation, but the underlying mechanisms remain largely unknown. Here, in rat hippocampal CA1 pyramidal cells under blockade of ionotropic glutamate receptors, we report that a single acetylcholine pulse and repeated depolarization activated a robust and enduring postsynaptic depolarization-induced enhancement of inhibition (DEI) that masked a presynaptic depolarization-induced suppression of inhibition (DSI). Increased cytosolic Ca2+ and M1-muscarinic receptor activation caused the rise in voltage-sensitive α5βγ2-containing γ-aminobutyric acid type-A receptors that generated DEI. In summary, this muscarinic-mediated activity-dependent plasticity rapidly transfers depolarization effects on inhibition from presynaptic suppression or DSI to postsynaptic enhancement or DEI, a change potentially relevant in behavior.
authors.affiliation: Instituto Cajal, CSIC, 28002 Madrid, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Domínguez
authors.affiliation: Instituto Cajal, CSIC, 28002 Madrid, Spain.|Depto. Anatomía, Histología y Neurociencia, Facultad de Medicina UAM, 28029 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Fernández de Sevilla
authors.affiliation: Instituto Cajal, CSIC, 28002 Madrid, Spain.
authors.forename: Washington
authors.initials: W
authors.lastname: Buño
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: C543264:Cnr1 protein, rat; D043884:Receptor, Cannabinoid, CB1; D043643:Receptor, Muscarinic M1; D043562:Receptors, G-Protein-Coupled; D011963:Receptors, GABA-A; D000109:Acetylcholine; D002118:Calcium
keywords: GABAA-LTP; GPCR activity; cytosolic Ca2+; negative feedback; α5βγ2-GABAARs