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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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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