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Genetic lesioning of histamine neurons increases sleep-wake fragmentation and reveals their contribution to modafinil-induced wakefulness
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zsz031.pdf | Published version | 13.63 MB | Adobe PDF | View/Open |
Title: | Genetic lesioning of histamine neurons increases sleep-wake fragmentation and reveals their contribution to modafinil-induced wakefulness |
Authors: | Yu, X Ma, Y Harding, E Yustos, R Vyssotski, A Franks, N Wisden, W |
Item Type: | Journal Article |
Abstract: | Acute chemogenetic inhibition of histamine (HA) neurons in adult mice induced nonrapid eye movement (NREM) sleep with an increased delta power. By contrast, selective genetic lesioning of HA neurons with caspase in adult mice exhibited a normal sleep–wake cycle overall, except at the diurnal start of the lights-off period, when they remained sleepier. The amount of time spent in NREM sleep and in the wake state in mice with lesioned HA neurons was unchanged over 24 hr, but the sleep–wake cycle was more fragmented. Both the delayed increase in wakefulness at the start of the night and the sleep–wake fragmentation are similar phenotypes to histidine decarboxylase knockout mice, which cannot synthesize HA. Chronic loss of HA neurons did not affect sleep homeostasis after sleep deprivation. However, the chronic loss of HA neurons or chemogenetic inhibition of HA neurons did notably reduce the ability of the wake-promoting compound modafinil to sustain wakefulness. Thus, part of modafinil’s wake-promoting actions arise through the HA system. |
Issue Date: | 5-Feb-2019 |
Date of Acceptance: | 29-Jan-2019 |
URI: | http://hdl.handle.net/10044/1/67232 |
DOI: | https://doi.org/10.1093/sleep/zsz031 |
ISSN: | 0161-8105 |
Publisher: | Oxford University Press (OUP) |
Start Page: | 1 |
End Page: | 13 |
Journal / Book Title: | Sleep |
Volume: | 42 |
Issue: | 5 |
Copyright Statement: | © Sleep Research Society 2019. Published by Oxford University Press [on behalf of the Sleep Research Society]. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Sponsor/Funder: | Wellcome Trust UK DRI Ltd Wellcome Trust Wellcome Trust |
Funder's Grant Number: | 107841/Z/15/Z 4050641385 107839/Z/15/Z 107841/Z/15/Z |
Keywords: | Science & Technology Life Sciences & Biomedicine Clinical Neurology Neurosciences Neurosciences & Neurology histamine histidine decarboxylase modafinil tuberomammillary nucleus caspase lesioning chemogenetics wakefulness NREM sleep TUBEROMAMMILLARY NUCLEUS CORTICAL ACTIVATION BRAIN HISTAMINE MICE HYPOTHALAMUS NARCOLEPSY AMPHETAMINE COGNITION RECEPTOR RELEASE NREM sleep caspase chemogenetics histamine histidine decarboxylase lesioning modafinil tuberomammillary nucleus wakefulness 06 Biological Sciences 11 Medical and Health Sciences 17 Psychology and Cognitive Sciences Neurology & Neurosurgery |
Publication Status: | Published |
Online Publication Date: | 2019-02-05 |
Appears in Collections: | Faculty of Natural Sciences |