title: Cell type-specific dependence of muscarinic signalling in mouse hippocampal stratum oriens interneurones.
abstract: Cholinergic signalling is critically involved in learning and memory processes in the hippocampus, but the postsynaptic impact of cholinergic modulation on morphologically defined subtypes of hippocampal interneurones remains unclear. We investigated the influence of muscarinic receptor (mAChR) activation on stratum oriens interneurones using whole-cell patch clamp recordings from hippocampal slices in vitro. Upon somatic depolarization, mAChR activation consistently enhanced firing frequency and produced large, sustained afterdepolarizations (ADPs) of stratum oriens-lacunosum moleculare (O-LM) interneurones. In contrast, stratum oriens cell types with axon arborization patterns different from O-LM cells not only lacked large muscarinic ADPs but also appeared to exhibit distinct responses to mAChR activation. The ADP in O-LM cells, mediated by M1/M3 receptors, was associated with inhibition of an M current, inhibition of a slow calcium-activated potassium current, and activation of a calcium-dependent non-selective cationic current (ICAT). An examination of ionic conductances generated by firing revealed that calcium entry through ICAT controls the emergence of the mAChR-mediated ADP. Our results indicate that cholinergic specializations are present within anatomically distinct subpopulations of hippocampal interneurones, suggesting that there may be organizing principles to cholinergic control of GABA release in the hippocampus.
authors.affiliation: Laboratory on Cellular and Synaptic Neurophysiology, Building 35, Rm 3C907, NICHD-LCSN, Bethesda, MD 20892, USA. lawrenjo@mail.nih.gov
authors.forename: J Josh
authors.initials: JJ
authors.lastname: Lawrence
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Statland
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Grinspan
authors.forename: Chris J
authors.initials: CJ
authors.lastname: McBain
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002799:Cholinergic Fibers / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D007395:Interneurons / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D043643:Receptor, Muscarinic M1 / Q000235:genetics / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D024681:Potassium Channels, Calcium-Activated; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D002118:Calcium