Prolonged stimulation of respiration by a new central neural mechanism

Millhorn, David E.; Eldridge, Frederíc L.; Waldrop, Tony G.

doi:10.1016/0034-5687(80)90025-0

Cited by 215 publications

(168 citation statements)

References 19 publications

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“…I believe that the raphe nuclei are a component of that mechanism. The long-term potentiation found following raphe obscurus stimulation was essentially identical in both time course and magnitude as that found following carotid body afferent stimulation (Millhorn et al 1980a). …”

Section: Resultssupporting

confidence: 56%

Stimulation of raphe (obscurus) nucleus causes long‐term potentiation of phrenic nerve activity in cat.

Millhorn¹

1986

The Journal of Physiology

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SUMMARY1. The respiratory response, measured as integrated phrenic nerve activity, during and for up to an hour following 10 min of continuous electrical stimulation of raphe obscurus was quantitated in anaesthetized, artificially ventilated cats whose carotid sinus nerves and vagus nerves had been cut. End-tidal PCO2 and body temperature were kept constant with servocontrollers.2. Stimulation of raphe obscurus caused a significant increase in both phrenic tidal activity and respiratory frequency that persisted following cessation of the stimulus. This persistent facilitation is referred to as 'long-term potentiation' of respiration.3. Control stimulations in the parenchyma of the medulla oblongata failed to stimulate respiration and cause the long-term potentiation.4. Both the direct facilitatory effects of raphe obscurus stimulation on phrenic nerve activity and the long-term potentiation of respiration following the stimulus were prevented by pre-treating cats with methysergide, a serotonin receptor antagonist.

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Section: Resultssupporting

confidence: 56%

Stimulation of raphe (obscurus) nucleus causes long‐term potentiation of phrenic nerve activity in cat.

Millhorn¹

1986

The Journal of Physiology

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“…5). This progressive augmentation is characteristic of some studies (Turner and Mitchell, 1997;Millhorn et al, 1980), and not others (Bach et al, 1996). Interestingly, GG LTF occurred without accompanying changes in minute ventilation or upper airway resistance during the recovery period.…”

Section: Ltf Of Genioglossusmentioning

confidence: 59%

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep

Chowdhuri

Pierchala

Aboubakr

et al. 2008

Respiratory Physiology & Neurobiology

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Episodic hypoxia (EH) is followed by increased ventilatory motor output in the recovery period indicative of long-term facilitation (LTF). We hypothesized that episodic hypoxia evokes LTF of genioglossus (GG) muscle activity in humans during non-rapid eye movement sleep (NREM) sleep. We studied 12 normal non-flow limited humans during stable NREM sleep. We induced 10 brief (3 minute) episodes of isocapnic hypoxia followed by 5 minutes of room air. Measurements were obtained during control, hypoxia, and at 5, 10, 20, 30 and 40 minutes of recovery, respectively, for minute ventilation (V̇I), supraglottic pressure (P SG ), upper airway resistance (R UA ) and phasic GG electromyogram (EMG GG ). In addition, sham studies were conducted on room air. During hypoxia there was a significant increase in phasic EMG GG (202.7±24.1% of control, p<0.01) and in V̇I (123.0 ±3.3% of control, p<0.05); however, only phasic EMG GG demonstrated a significant persistent increase throughout recovery (198.9±30.9%, 203.6±29.9% and 205.4±26.4% of control, at 5, 10, and 20 minutes of recovery, respectively, p<0.01). In multivariate regression analysis, age and phasic EMG GG activity during hypoxia were significant predictors of EMG GG at recovery 20 minutes. No significant changes in any of the measured parameters were noted during sham studies. Conclusion: 1) EH elicits LTF of GG in normal non-flow limited humans during NREM sleep, without ventilatory or mechanical LTF. 2) GG activity during the recovery period correlates with the magnitude of GG activation during hypoxia, and inversely with age.

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“…Serotonergic neurons have been implicated in other respiratory reflexes, including long-term facilitation of respiration by repeated exposure to hypoxia. Stimulation of raphe obscurus neurons in anesthetized cats leads to long-term potentiation of phrenic nerve output (Millhorn, 1986), which is thought to represent the source of facilitation of respiration after either direct stimulation of carotid body afferents (Millhorn et al, 1980a(Millhorn et al, , 1980b or exposure to hypoxia (Olson et al, 2001). Further, depletion of spinal serotonin leads to an attenuation or even abolishment of long-term facilitation in anesthetized rats (BakerHerman and Mitchell, 2002).…”

Section: Discussionmentioning

confidence: 99%

Activity ofTachykinin1-ExpressingPet1Raphe Neurons Modulates the Respiratory Chemoreflex

et al. 2017

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Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1, referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO 2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO 2 . Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei.

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Prolonged stimulation of respiration by a new central neural mechanism

Cited by 215 publications

References 19 publications

Stimulation of raphe (obscurus) nucleus causes long‐term potentiation of phrenic nerve activity in cat.

Stimulation of raphe (obscurus) nucleus causes long‐term potentiation of phrenic nerve activity in cat.

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep

Activity ofTachykinin1-ExpressingPet1Raphe Neurons Modulates the Respiratory Chemoreflex

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