title: Slow Bursting Neurons of Mouse Cortical Layer 6b Are Depolarized by Hypocretin/Orexin and Major Transmitters of Arousal.
abstract: Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previously recorded in different layers of cortical brain slices. It has been suggested that such neurons could contribute to the generation of alternating UP and DOWN states, a pattern of activity seen during slow-wave sleep. Here, we show that in layer 6b (L6b), known from our previous studies to contain neurons highly responsive to the wake-promoting transmitter hypocretin/orexin (hcrt/orx), there is a set of neurons, endowed with distinct intrinsic properties, which displayed a strong propensity to fire spontaneously in rhythmic bursts. In response to small depolarizing steps, they responded with a delayed firing of action potentials which, upon higher depolarizing steps, invariably inactivated and were followed by a depolarized plateau potential and a depolarizing afterpotential. These cells also displayed a strong hyperpolarization-activated rectification compatible with the presence of an I h current. Most L6b neurons with such properties were able to fire spontaneously in bursts. Their bursting activity was of intrinsic origin as it persisted not only in presence of blockers of ionotropic glutamatergic and GABAergic receptors but also in a condition of complete synaptic blockade. However, a small number of these neurons displayed a mix of intrinsic bursting and synaptically driven recurrent UP and DOWN states. Most of the bursting L6b neurons were depolarized and excited by hcrt/orx through a direct postsynaptic mechanism that led to tonic firing and eventually inactivation. Similarly, they were directly excited by noradrenaline, histamine, dopamine, and neurotensin. Finally, the intracellular injection of these cells with dye and their subsequent Neurolucida reconstruction indicated that they were spiny non-pyramidal neurons. These results lead us to suggest that the propensity for slow rhythmic bursting of this set of L6b neurons could be directly impeded by hcrt/orx and other wake-promoting transmitters.
authors.affiliation: Département des neurosciences fondamentales, Centre Médical Universitaire , Geneva , Switzerland.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Wenger Combremont
authors.affiliation: Département des neurosciences fondamentales, Centre Médical Universitaire, Geneva, Switzerland; Centre de médecine du sommeil, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bayer
authors.affiliation: Département des neurosciences fondamentales, Centre Médical Universitaire , Geneva , Switzerland.
authors.forename: Anouk
authors.initials: A
authors.lastname: Dupré
authors.affiliation: Département des neurosciences fondamentales, Centre Médical Universitaire , Geneva , Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Mühlethaler
authors.affiliation: Département des neurosciences fondamentales, Centre Médical Universitaire , Geneva , Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Serafin
keywords: acetylcholine; arousal; dopamine; histamine; neurotensin; noradrenaline; sleep