A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia

Kaur, Satvinder; Wang, Joshua; Ferrari, Loris; Thankachan, Stephen; Kroeger, Daniel; Venner, Anne; Lazarus, Michael; Wellman, Andrew; Arrigoni, Elda; Fuller, Patrick M.; Saper, Clifford B.

doi:10.1016/j.neuron.2017.10.009

Cited by 128 publications

(193 citation statements)

References 81 publications

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“…One or more months following surgery, mice were placed in a chamber ( Figure 3B) where they were exposed to brief (30s) elevations in the ambient level of CO2, cycling every 5 minutes for four hours during the light period. Under baseline conditions, latency to cortical arousal from NREM was reliably induced by increasing CO2 levels from 1 % to 10% inside the chamber (15.99±1.23 s; Figure 4A), similar to that reported in Kaur et al, (2013Kaur et al, ( , 2017.…”

Section: Optogenetic Inhibition Of Bf Pv Neurons Inhibits Arousals Dusupporting

confidence: 80%

Basal forebrain parvalbumin neurons mediate arousals from sleep induced by hypercarbia or auditory stimuli

Mckenna

Thankachan

Uygun

et al. 2019

Preprint

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SUMMARYBrief arousals from sleep in patients with sleep apnea and other disorders prevent restful sleep, and contribute to cognitive, metabolic and physiologic dysfunction. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments. The basal forebrain (BF) receives inputs from many nuclei of the ascending arousal system. These inputs include the brainstem parabrachial neurons which promote arousal in response to elevated blood carbon dioxide levels, as seen in sleep apnea. Optical inhibition of the terminals of parabrachial neurons in the BF impairs cortical arousals to hypercarbia, but which cell types within the BF mediate cortical arousals in response to hypercarbia or other sensory stimuli is unknown. Here using optogenetic techniques in mice, we show that BF parvalbumin (PV) neurons fulfill several criteria for a system mediating brief arousals from sleep. Optical stimulation of BF PV neurons during the light period, when mice normally sleep, caused rapid transitions to wakefulness and increased wake bout durations. Unlike many other ascending arousal systems, arousals induced by stimulation of BF PV neurons were brief, resulting in only a small (13.6%) increase in the total amount of wakefulness. Bilateral optical inhibition of BF PV neurons increased the latency to arousal produced by hypercarbia or auditory stimuli. Thus, BF PV neurons are an important component of the brain circuitry which generates brief arousals from sleep in response to internal and external sensory stimuli.

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Section: Optogenetic Inhibition Of Bf Pv Neurons Inhibits Arousals Dusupporting

confidence: 80%

Basal forebrain parvalbumin neurons mediate arousals from sleep induced by hypercarbia or auditory stimuli

Mckenna

Thankachan

Uygun

et al. 2019

Preprint

Self Cite

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“…Inhibition of CGRP-expressing neurons in elPBN restored food intake in these animals (Carter et al, 2013) and also prevented anorexia in visceral illness, malaise, and cancer cachexia (Carter et al, 2013;Campos et al, 2017). Together with evidence that CGRP-expressing lPBN neurons projecting to CeA have a significant role in the affective dimension of pain and contribute to hyperalgesia in persistent pain states (Neugebauer et al, 2004), and that these neurons have a role in other protective responses (Mu et al, 2017), for example, chemosensory arousal and itch (Kaur et al, 2017), it has been proposed that CGRP-expressing neurons in elPBN generate a multimodal threat signal that engages defensive behaviors (Palmiter, 2018).…”

Section: Pbn As a Contributor To General Alarm With A Specific Rolementioning

confidence: 64%

Parabrachial Complex: A Hub for Pain and Aversion

et al. 2019

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The parabrachial nucleus (PBN) has long been recognized as a sensory relay receiving an array of interoceptive and exteroceptive inputs relevant to taste and ingestive behavior, pain, and multiple aspects of autonomic control, including respiration, blood pressure, water balance, and thermoregulation. Outputs are known to be similarly widespread and complex. How sensory information is handled in PBN and used to inform different outputs to maintain homeostasis and promote survival is only now being elucidated. With a focus on taste and ingestive behaviors, pain, and thermoregulation, this review is intended to provide a context for analysis of PBN circuits involved in aversion and avoidance, and consider how information of various modalities, interoceptive and exteroceptive, is processed within PBN and transmitted to distinct targets to signal challenge, and to engage appropriate behavioral and physiological responses to maintain homeostasis.

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“…The identification of the Tac1 brainstem circuit provides new insight into how responses to noxious stimuli may be controlled by top-down input. A wide variety of brain regions send projections to the PBNl ( Figure S5) and competing need states are known to potently modulate pain responses (Alhadeff et al, 2018;Kaur et al, 2017;Roman et al, 2016;Sohn et al, 2013). Better characterization of the inputs to PBNl Tac1 and MdD Tac1 neurons should offer important insight into the coordination of pain responses with other biological needs (e.g., feeding, reproduction, avoiding predators, etc.)…”

Section: Discussionmentioning

confidence: 99%