title: Mixed mode oscillations in mouse spinal motoneurons arise from a low excitability state.
abstract: We explain the mechanism that elicits the mixed mode oscillations (MMOs) and the subprimary firing range that we recently discovered in mouse spinal motoneurons. In this firing regime, high-frequency subthreshold oscillations appear a few millivolts below the spike voltage threshold and precede the firing of a full blown spike. By combining intracellular recordings in vivo (including dynamic clamp experiments) in mouse spinal motoneurons and modeling, we show that the subthreshold oscillations are due to the spike currents and that MMOs appear each time the membrane is in a low excitability state. Slow kinetic processes largely contribute to this low excitability. The clockwise hysteresis in the I-F relationship, frequently observed in mouse motoneurons, is mainly due to a substantial slow inactivation of the sodium current. As a consequence, less sodium current is available for spiking. This explains why a large subprimary range with numerous oscillations is present in motoneurons displaying a clockwise hysteresis. In motoneurons whose I-F curve exhibits a counterclockwise hysteresis, it is likely that the slow inactivation operates on a shorter time scale and is substantially reduced by the de-inactivating effect of the afterhyperpolarization (AHP) current, thus resulting in a more excitable state. This accounts for the short subprimary firing range with only a few MMOs seen in these motoneurons. Our study reveals a new role for the AHP current that sets the membrane excitability level by counteracting the slow inactivation of the sodium current and allows or precludes the appearance of MMOs.
authors.affiliation: Laboratoire de Neurophysique et Physiologie, Université Paris Descartes, Institut des Neurosciences et de la Cognition, Centre National de la Recherche Scientifique UMR 8119, Paris 75006, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Iglesias
authors.forename: Claude
authors.initials: C
authors.lastname: Meunier
authors.forename: Marin
authors.initials: M
authors.lastname: Manuel
authors.forename: Yulia
authors.initials: Y
authors.lastname: Timofeeva
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delestrée
authors.forename: Daniel
authors.initials: D
authors.lastname: Zytnicki
mesh_terms: D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D055724:Electrophysiological Phenomena; D005260:Female; D008566:Membranes / Q000502:physiology; D051379:Mice; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*
chemical_list: D015222:Sodium Channels