Basal Forebrain Parvalbumin Neurons Mediate Arousals from Sleep Induced by Hypercarbia or Auditory Stimuli

The ability to rapidly arouse from sleep is important for survival. However, increased arousals in patients with sleep apnea and other disorders prevent restful sleep and contribute to cognitive, metabolic, and physiologic dysfunction [1, 2]. Little is currently known about which neural systems medi...

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Published in:Current biology 2020-06, Vol.30 (12), p.2379-2385.e4
Main Authors: McKenna, James T., Thankachan, Stephen, Uygun, David S., Shukla, Charu, McNally, James M., Schiffino, Felipe L., Cordeira, Joshua, Katsuki, Fumi, Zant, Janneke C., Gamble, Mackenzie C., Deisseroth, Karl, McCarley, Robert W., Brown, Ritchie E., Strecker, Robert E., Basheer, Radhika
Format: Article
Language:English
Subjects:
Acoustic Stimulation
Animal Feed - analysis
Animals
ArchT
Arousal - physiology
ascending reticular activating system
basal forebrain
Basal Forebrain - physiology
Carbohydrates - administration & dosage
channelrhodopsin2
cortical arousal
Diet
GABAergic
hypercarbia
Mice
Neurons - physiology
parvalbumin
Parvalbumins - metabolism
Sleep - physiology
sleep apnea
sleep-wake
Wakefulness - physiology
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Summary:The ability to rapidly arouse from sleep is important for survival. However, increased arousals in patients with sleep apnea and other disorders prevent restful sleep and contribute to cognitive, metabolic, and physiologic dysfunction [1, 2]. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments that restore normal sleep. The basal forebrain (BF) receives inputs from many nuclei of the ascending arousal system, including the brainstem parabrachial neurons, which promote arousal in response to elevated blood carbon dioxide levels, as seen in sleep apnea [3]. Optical inhibition of the terminals of parabrachial neurons in the BF impairs cortical arousals to hypercarbia [4], but which BF cell types mediate cortical arousals in response to hypercarbia or other sensory stimuli is unknown. Here, we tested the role of BF parvalbumin (PV) neurons in arousal using optogenetic techniques in mice. Optical stimulation of BF-PV neurons produced rapid transitions to wakefulness from non-rapid eye movement (NREM) sleep but did not affect REM-wakefulness transitions. Unlike previous studies of BF glutamatergic and cholinergic neurons, arousals induced by stimulation of BF-PV neurons were brief and only slightly increased total wake time, reminiscent of clinical findings in sleep apnea [5, 6]. Bilateral optical inhibition of BF-PV neurons increased the latency to arousal produced by exposure to hypercarbia or auditory stimuli. Thus, BF-PV neurons are an important component of the brain circuitry that generates brief arousals from sleep in response to stimuli, which may indicate physiological dysfunction or danger to the organism. •Optical stimulation of basal forebrain parvalbumin neurons caused rapid arousals•Arousals induced by stimulation of basal forebrain parvalbumin neurons were brief•Optical inhibition suppressed arousals in response to increased carbon dioxide•Optical inhibition suppressed arousals elicited by auditory stimuli Brief arousals from sleep in sleep apnea and other disorders hinder the restorative effects of sleep. Using optogenetic techniques in mice, McKenna et al. identify basal forebrain parvalbumin neurons as an important contributor to brief arousals from sleep elicited by increased carbon dioxide levels or acoustic stimuli.
ISSN:0960-9822
1879-0445
DOI:10.1016/j.cub.2020.04.029