title: Effects of Hypocretin/Orexin and Major Transmitters of Arousal on Fast Spiking Neurons in Mouse Cortical Layer 6B.
abstract: Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequency cortical rhythms during the waking state. We previously showed that cortical layer 6b (L6b) was a specific target for the wake-promoting transmitter, hypocretin/orexin (hcrt/orx). Here, we have investigated whether L6b FS cells were sensitive to hcrt/orx and other transmitters associated with cortical activation. Recordings were thus made from L6b FS cells in either wild-type mice or in transgenic mice in which GFP-positive GABAergic cells are parvalbumin positive. Whereas in a control condition hcrt/orx induced a strong increase in the frequency, but not amplitude, of spontaneous synaptic currents, in the presence of TTX, it had no effect at all on miniature synaptic currents. Hcrt/orx effect was thus presynaptic although not by an action on glutamatergic terminals but rather on neighboring cells. In contrast, noradrenaline and acetylcholine depolarized and excited these cells through a direct postsynaptic action. Neurotensin, which is colocalized in hcrt/orx neurons, also depolarized and excited these cells but the effect was indirect. Morphologically, these cells exhibited basket-like features. These results suggest that hcrt/orx, noradrenaline, acetylcholine, and neurotensin could contribute to high-frequency cortical activity through an action on L6b GABAergic FS cells.
authors.affiliation: Département des Neurosciences Fondamentales, Centre Médical Universitaire, Genève, Suisse.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Wenger Combremont
authors.affiliation: Département des Neurosciences Fondamentales, Centre Médical Universitaire, Genève, Suisse Centre de Médecine du Sommeil, Hôpitaux Universitaires de Genève, Genève, Suisse.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bayer
authors.affiliation: Département des Neurosciences Fondamentales, Centre Médical Universitaire, Genève, Suisse.
authors.forename: Anouk
authors.initials: A
authors.lastname: Dupré
authors.affiliation: Département des Neurosciences Fondamentales, Centre Médical Universitaire, Genève, Suisse.
authors.forename: Michel
authors.initials: M
authors.lastname: Mühlethaler
authors.affiliation: Département des Neurosciences Fondamentales, Centre Médical Universitaire, Genève, Suisse.
authors.forename: Mauro
authors.initials: M
authors.lastname: Serafin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000502:physiology; D059330:GABAergic Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D000068797:Orexins / Q000378:metabolism* / Q000494:pharmacology; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013003:Somatosensory Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D018377:Neurotransmitter Agents; D000068797:Orexins; D010320:Parvalbumins; D049452:Green Fluorescent Proteins; D009496:Neurotensin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D000109:Acetylcholine; D009638:Norepinephrine
keywords: acetylcholine; arousal; neurotensin; noradrenaline; sleep