OSCR

Cortical layer 6b mediates state-dependent changes in brain activity and effects of orexin on waking and sleep.

Overview

  1. Department of Physiology, Anatomy and Genetics, University of Oxford Oxford United Kingdom
  2. Sleep and Circadian Neuroscience Institute, University of Oxford Oxford United Kingdom
  3. Kavli Institute for Nanoscience Discovery, University of Oxford Oxford United Kingdom
  4. University Hospital of Psychiatry and Psychotherapy, University of Bern Bern Switzerland
  5. Department of Pharmacology, University of Oxford Oxford United Kingdom
Institutions: University of Oxford (United Kingdom); University of Bern (Switzerland)
Journal: eLife, volume 14, article RP106992
Dates: published online 8 September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7554/elife.106992 · PMID 42706848 · PMCID PMC13553069 · OpenAlex W4413777301
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: EEG (modality), mouse (organism)
Methods: Connectivity, Spectral & time-frequency, Statistics, Preprocessing, Physiology & signal measures
Keywords: Drd1a-Cre, subplate neurons, cortical layer 6b, orexin, arousal, brain state control, Mouse
MeSH: Brain*, Cerebral Cortex*, Orexins*, Sleep*, Wakefulness*, Animals, Electroencephalography, Male, Mice, Neurons, Sleep Deprivation (* major topic)
Journal subjects: Neuroscience
Topic: Sleep and Wakefulness Research (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: Medical Research Centre (MR/W029073/1, MR/S01134X/1, MR/V013238/1); BBSRC (BB/M011224/1, BB/X008711/1); St John's College Research Centre (Medium SJC Research Centre Grant); Wellcome Trust (10.35802/227093, 10.35802/206500, 10.35802/203971, 10.35802/224083); O'Sullivan Family Graduate Scholarship (O'Sullivan Family Graduate Scholarship); Rhodes Scholarships (Rhodes Scholarship Canada); Clarendon Fund (Clarendon Graduate Studentship); Goodger and Schorstein Scholarship (Goodger and Schorstein Scholarship); NC3Rs studentship (NC/S001689/1); Exeter College Oxford (Staines Medical Research Fellowship at Exeter College Oxford)
Citations: not cited yet (Europe PMC); 104 references in the paper
Research resources: RRID:SCR_016854, VisuAlign RRID:SCR_017978

Abstract

One of the most distinctive features of the mammalian cerebral cortex is its laminar structure. Of all cortical layers, layer 6b (L6b) is by far the least studied, despite exhibiting direct sensitivity to orexin and having widespread connectivity, suggesting an important role in regulating cortical oscillations and brain state. We performed chronic electroencephalogram (EEG) recordings in mice in which a subset of L6b neurons was conditionally ‘silenced’, during undisturbed conditions, after sleep deprivation (SD), and after intracerebroventricular (ICV) administration of orexin. While the total amount of waking and sleep or the response to SD were not altered, L6b-silenced mice showed a slowing of theta frequency (6–9 Hz) during wake and rapid eye movement (REM) sleep, and a marked reduction of total EEG power, especially in non-rapid eye movement (NREM) sleep. The infusion of orexin A increased wakefulness in both genotypes, but subsequent levels of EEG slow-wave activity during NREM sleep were lower in L6b-silenced animals in the occipital derivation. In summary, these results demonstrate a role for cortical L6b in state-dependent brain oscillations and in the response to orexinergic neurotransmission. Our findings provide new insights in functions of L6b neurons and could inform the understanding of abnormal regulation of brain states in neurodevelopmental and psychiatric disorders.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

Data can be accessed through these links: Analysis: https://doi.org/10.6084/m9.figshare.31830526. EEG spectra: https://doi.org/10.6084/m9.figshare.31830520. Histology: https://doi.org/10.6084/m9.figshare.31830289. Vigilance state annotation: https://doi.org/10.6084/m9.figshare.31375441. Matlab scripts and functions: Resampling_Feb2022_20241027.m: This script resamples the EEG data that have been exported from the TDT recording software. It uses the TDTSDK Matlab package that is provided by TDT. The script loops through all animals, recording days and channels, obtains the original sampling rate from the raw data tank and resamples the signals to 256 Hz. The signals are saved per animal, recording day and EEG channel. BL_PSDperVS_fromunfilteredfiles_20241027.m: This script calculates EEG spectral power density per epoch with the PWelch function in Matlab. It loads the signals that have been exported from the TDT software and resampled in Matlab. It loops through all animals and recording days individually. The signal is zero padded if it is shorter than 24 hours and the signal is cut off at 24 hours if it is longer than 24 hours. There is the option to apply a notch filter, which is specified in the top lines in the script. The result is saved in a file per animal, per recording day and per channel (frontal EEG, occipital EEG). SleepEpisodes: This function finds the number and duration of uninterrupted episodes of NREM sleep, REM sleep, and wakefulness, using preset variables such as the maximal duration of interruptions that are allowed. BriefAwakenings: This function finds the number of brief awakenings, short stretches of epochs scored as wakefulness during episodes of sleep. The maximal duration of interruptions that are allowed to still classify the sleep episode as a single episode despite the interruption (and the interruption not as a new wake episode) are specified in the top lines of the script. EEG data: Baseline & sleep dep recording info: Information file that provides information on the Baseline and Sleep deprivation experiment. Orexin ICV schedule: Information file that provides information on the orexin intracerebroventricular (ICV) infusion experiment. Orexin spectra excluded animals: Lists excluded animals for spectral analysis including analysis of slow wave activity. We decided to exclude general spectral analysis, because the number of remaining animals was too low. OutputVSch: Output from SleepSign: per animal, EEG (1 = frontal, 2=occipital), and per day for every epoch the annotation from manual sleep scoring and spectra exported from SleepSign (for spectral analysis, PWelch spectra calculated directly from raw data files in Matlab were used instead). 1. Baseline: "C1" etc refers to animal name codes (data was recorded in two cohorts, C and D); number "1" refers to baseline file; "eeg1" and "eeg2" to frontal and occipital EEG derivation, respectively. 2. Sleep deprivation: as above; number "2" behind animal name codes refers to sleep deprivation file. 3. Orexin: "F1" etc refers to animal name codes (experiment was recorded in 4 cohorts F,G,H,I); four-character code refers to infusion (either INF1-4 or a four-digit date code; key to decoding can be found in the Orexin ICV study file); "eeg1" and "eeg2" to frontal and occipital EEG derivation, respectively. PwelchPSD: EEG spectral power density calculated with PWelch function in Matlab. Naming convention: no notch filter was applied, and this is also specified in the file name. 1. Baseline: C1" etc refers to animal name codes (data was recorded in two cohorts, C and D); date "0202" refers to baseline file for C cohort and "0224" refers to baseline file for D cohort, "ch1" and "ch2" to frontal and occipital EEG derivation, respectively2. Sleep deprivation: C1" etc refers to animal name codes (data was recorded in two cohorts, C and D); date "0203" refers to sleep deprivation file for C cohort and "0225" refers to sleep deprivation file for D cohort, "ch1" and "ch2" to frontal and occipital EEG derivation, respectively. Histology: Analysis 2 - Densities/DCST_Drd1a-Cplx3_Cell-Densities.prism: Compares Drd1a-Cre positive cell densities across layers. Images: Image files as TIFFs and PNGs. Prism files. Baseline_Sleeparchitecture: Prism file with statistical analysis of sleep architecture parameters. All electrophysiological and immunohistochemical data have been deposited as supplementary material. Figure 1—source data 1. Inter-layer pairwise comparisons. Figure 1—source data 2. Inter-region pairwise comparisons. Figure 3—source data 1. Comparison of EEG spectra from L6b silenced and control animals across the full frequency range recorded. Figure 4—source data 1. One sample t and Wilcoxon test of Wake during SD Frontal EEG Mean Controls. Figure 4—source data 2. One sample t and Wilcoxon test of Wake during SD Frontal EEG Mean L6b silenced. Figure 4—source data 3. One sample t and Wilcoxon test of Wake during SD Occipital EEG Mean Controls. Figure 4—source data 4. One sample t and Wilcoxon test of Wake during SD Occipital EEG Mean L6b silenced.

The following datasets were generated:

MeijerE 2026Meijer et al Layer 6b mediates state-dependent changes in brain activity and effects of orexin on waking and sleep - EEG SPECTRAfigshare10.6084/m9.figshare.31830520PMC1355306942706848

MeijerE 2026Meijer et al Layer 6b mediates state-dependent changes in brain activity and effects of orexin on waking and sleep - HISTOLOGY DATAfigshare10.6084/m9.figshare.31830289PMC1355306942706848

MeijerE 2026Meijer et al Layer 6b mediates state-dependent changes in brain activity and effects of orexin on waking and sleep - VIGILANCE STATE ANNOTATIONfigshare10.6084/m9.figshare.31375441PMC1355306942706848

MeijerE 2026Meijer et al Layer 6b mediates state-dependent changes in brain activity and effects of orexin on waking and sleep - ANALYSIS FILESfigshare10.6084/m9.figshare.31830526PMC1355306942706848

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 12 authors, 7 keywords, 11 MeSH terms, 10 funders, 104 references, 2 RRIDs.

Cite

This paper

Meijer, E. J., Mueller, M., Krone, L. B., Yamagata, T., Hoerder-Suabedissen, A., Wilcox, S., Alfonsa, H., Chakrabarty, A., Guidi, L., Oliver, P. L., Vyazovskiy, V. V., & Molnar, Z. (2026). Cortical layer 6b mediates state-dependent changes in brain activity and effects of orexin on waking and sleep. eLife, 14, RP106992. https://doi.org/10.7554/elife.106992

BibTeX

@article{meijer2026cortical,
author = {Meijer, Elise J and Mueller, Marissa and Krone, Lukas B and Yamagata, Tomoko and Hoerder-Suabedissen, Anna and Wilcox, Sian and Alfonsa, Hannah and Chakrabarty, Atreyi and Guidi, Luiz and Oliver, Peter L and Vyazovskiy, Vladyslav V and Molnar, Zoltan},
title = {{Cortical layer 6b mediates state-dependent changes in brain activity and effects of orexin on waking and sleep}},
journal = {eLife},
year = {2026},
month = sep,
volume = {14},
pages = {RP106992},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/elife.106992},
url = {https://doi.org/10.7554/elife.106992},
pmid = {42706848},
pmcid = {PMC13553069}
}

RIS

TY - JOUR
AU - Meijer, Elise J
AU - Mueller, Marissa
AU - Krone, Lukas B
AU - Yamagata, Tomoko
AU - Hoerder-Suabedissen, Anna
AU - Wilcox, Sian
AU - Alfonsa, Hannah
AU - Chakrabarty, Atreyi
AU - Guidi, Luiz
AU - Oliver, Peter L
AU - Vyazovskiy, Vladyslav V
AU - Molnar, Zoltan
TI - Cortical layer 6b mediates state-dependent changes in brain activity and effects of orexin on waking and sleep
T2 - eLife
J2 - eLife
PY - 2026
DA - 2026/09/08
VL - 14
SP - RP106992
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/elife.106992
UR - https://doi.org/10.7554/elife.106992
LA - en
ER -

CSL-JSON

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