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A distinct class of slow (~0.2–2 Hz)) intrinsically bursting layer 5 pyramidal neurons determines UP/DOWN state dynamics in the neocortex

Lorincz, Magor L., Gunner, David, Bao, Ying, Connelly, William M., Isaac, John T. R., Hughes, Stuart W. and Crunelli, Vincenzo ORCID: 2015. A distinct class of slow (~0.2–2 Hz)) intrinsically bursting layer 5 pyramidal neurons determines UP/DOWN state dynamics in the neocortex. Journal of Neuroscience 35 (14) , pp. 5442-5458. 10.1523/JNEUROSCI.3603-14.2015

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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 andfoundthat an electrophysiologically distinct subset of layer 5 regular spiking pyramidal neuronsfires earlier duringthe 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: acetylcholine; inhibition; muscarinic; rhythmic bursting; slow waves
Publisher: Society for Neuroscience
ISSN: 1529-2401
Funders: Wellcome Trust
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 4 February 2015
Last Modified: 05 May 2023 18:11

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