title: A distinct class of slow (~0.2-2 Hz) intrinsically bursting layer 5 pyramidal neurons determines UP/DOWN state dynamics in the neocortex.
abstract: During sleep and anesthesia, neocortical neurons exhibit rhythmic UP/DOWN membrane potential states. Although UP states are maintained by synaptic activity, the mechanisms that underlie the initiation and robust rhythmicity of UP states are unknown. Using a physiologically validated model of UP/DOWN state generation in mouse neocortical slices whereby the cholinergic tone present in vivo is reinstated, we show that the regular initiation of UP states is driven by an electrophysiologically distinct subset of morphologically identified layer 5 neurons, which exhibit intrinsic rhythmic low-frequency burst firing at ~0.2-2 Hz. This low-frequency bursting is resistant to block of glutamatergic and GABAergic transmission but is absent when slices are maintained in a low Ca(2+) medium (an alternative, widely used model of cortical UP/DOWN states), thus explaining the lack of rhythmic UP states and abnormally prolonged DOWN states in this condition. We also characterized the activity of various other pyramidal and nonpyramidal neurons during UP/DOWN states and found that an electrophysiologically distinct subset of layer 5 regular spiking pyramidal neurons fires earlier during the onset of network oscillations compared with all other types of neurons recorded. This study, therefore, identifies an important role for cell-type-specific neuronal activity in driving neocortical UP states.
authors: Research Group for Cellular and Network Neurophysiology of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, 6726 Szeged, Hungary, Neuroscience Division, School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom, and mlorincz@bio.u-szeged.hu.
authors: Magor L
authors: http://orcid.org/0000-0001-5240-1904
authors: ML
authors: Lőrincz
authors: Lilly Research Laboratories, Surrey GU20 6PH, United Kingdom.
authors: David
authors: D
authors: Gunner
authors: Neuroscience Division, School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom, and.
authors: Ying
authors: Y
authors: Bao
authors: Neuroscience Division, School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom, and.
authors: William M
authors: http://orcid.org/0000-0002-0986-6260
authors: WM
authors: Connelly
authors: Lilly Research Laboratories, Surrey GU20 6PH, United Kingdom.
authors: John T R
authors: JT
authors: Isaac
authors: Lilly Research Laboratories, Surrey GU20 6PH, United Kingdom.
authors: Stuart W
authors: SW
authors: Hughes
authors: Neuroscience Division, School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom, and.
authors: Vincenzo
authors: V
authors: Crunelli
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004569:Electroencephalography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010507:Periodicity; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; C070614:neurobiotin; D001710:Biotin; C013411:biocytin; D008239:Lysine; D002118:Calcium
keywords: acetylcholine; inhibition; muscarinic; rhythmic bursting; slow waves