Prolonged stimulation for respiration by endogenous central serotonin

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

doi:10.1016/0034-5687(80)90113-9

Cited by 207 publications

(146 citation statements)

References 27 publications

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“…State-dependent changes in ventilation in response to local perturbations of raphé neurons support the hypothesis that midline neurons are elements of a distributed brainstem system of central chemoreceptors (Nattie & Li 2009), as well as modulators of central chemoreceptors at other sites, including the retrotrapezoid nucleus (Mulkey et al 2004;Dias et al 2008). Stimulation of peripheral chemoreceptors also evokes changes in raphé neuron activity (Morris et al 1996a, and repeated intermittent stimulation of peripheral carotid body chemoreceptors or medullary raphé neurons can induce a long-term facilitation of phrenic nerve amplitude and cycling frequency (Millhorn et al 1980;Morris et al 1996aMorris et al ,b, 2001Mitchell et al 2001). Similar patterns of central chemoreceptor stimulation do not produce this respiratory memory (Millhorn 1986).…”

Section: Introductionmentioning

confidence: 53%

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Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network

Nuding

Segers

Shannon

et al. 2009

Phil. Trans. R. Soc. B

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The brainstem network for generating and modulating the respiratory motor pattern includes neurons of the medullary ventrolateral respiratory column (VRC), dorsolateral pons (PRG) and raphé nuclei. Midline raphé neurons are proposed to be elements of a distributed brainstem system of central chemoreceptors, as well as modulators of central chemoreceptors at other sites, including the retrotrapezoid nucleus. Stimulation of the raphé system or peripheral chemoreceptors can induce a long-term facilitation of phrenic nerve activity; central chemoreceptor stimulation does not. The network mechanisms through which each class of chemoreceptor differentially influences breathing are poorly understood. Microelectrode arrays were used to monitor sets of spike trains from 114 PRG, 198 VRC and 166 midline neurons in six decerebrate vagotomized cats; 356 were recorded during sequential stimulation of both receptor classes via brief CO 2 -saturated saline injections in vertebral (central) and carotid arteries (peripheral). Seventy neurons responded to both stimuli. More neurons were responsive only to peripheral challenges than those responsive only to central chemoreceptor stimulation (PRG, 20 : 4; VRC, 41 : 10; midline, 25 : 13). Of 16 474 pairs of neurons evaluated for short-time scale correlations, similar percentages of reference neurons in each brain region had correlation features indicative of a specific interaction with at least one target neuron: PRG (59.6%), VRC (51.0%) and raphé nuclei (45.8%). The results suggest a brainstem network architecture with connectivity that shapes the respiratory motor pattern via overlapping circuits that modulate central and peripheral chemoreceptor-mediated influences on breathing.

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Section: Introductionmentioning

confidence: 53%

“…(b) Other relationships to previous studies Long-term respiratory facilitation can be induced by repeated brief stimulation of peripheral chemoreceptors or medullary raphé neurons (Millhorn et al 1980;Morris et al 1996aMorris et al ,b, 2001; Mitchell et al…”

Section: Discussionmentioning

confidence: 76%

Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network

Nuding

Segers

Shannon

et al. 2009

Phil. Trans. R. Soc. B

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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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“…In normoxic intervals between successive hypoxic episodes, a progressive windup of respiratory activity is often observed, reflecting the development of LTF (162,197). After 3-10 hypoxic episodes, LTF is expressed as a persistent elevation of respiratory motor output, lasting many minutes to hours.…”

Section: Hypoxia-induced Respiratory Plasticity (Adult)mentioning

confidence: 99%

“…After 3-10 hypoxic episodes, LTF is expressed as a persistent elevation of respiratory motor output, lasting many minutes to hours. Phrenic LTF is a central neural mechanism (162,166) elicited by intermittent but not continuous hypoxia (9). LTF requires spinal serotonin receptor activation and spinal protein synthesis (10), enhancing synaptic inputs to phrenic motoneurons (64).…”

Section: Hypoxia-induced Respiratory Plasticity (Adult)mentioning

confidence: 99%

Invited Review: Neuroplasticity in respiratory motor control

Mitchell

Johnson

2003

Journal of Applied Physiology

354

313

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Although recent evidence demonstrates considerable neuroplasticity in the respiratory control system, a comprehensive conceptual framework is lacking. Our goals in this review are to define plasticity (and related neural properties) as it pertains to respiratory control and to discuss potential sites, mechanisms, and known categories of respiratory plasticity. Respiratory plasticity is defined as a persistent change in the neural control system based on prior experience. Plasticity may involve structural and/or functional alterations (most commonly both) and can arise from multiple cellular/synaptic mechanisms at different sites in the respiratory control system. Respiratory neuroplasticity is critically dependent on the establishment of necessary preconditions, the stimulus paradigm, the balance between opposing modulatory systems, age, gender, and genetics. Respiratory plasticity can be induced by hypoxia, hypercapnia, exercise, injury, stress, and pharmacological interventions or conditioning and occurs during development as well as in adults. Developmental plasticity is induced by experiences (e.g., altered respiratory gases) during sensitive developmental periods, thereby altering mature respiratory control. The same experience later in life has little or no effect. In adults, neuromodulation plays a prominent role in several forms of respiratory plasticity. For example, serotonergic modulation is thought to initiate and/or maintain respiratory plasticity following intermittent hypoxia, repeated hypercapnic exercise, spinal sensory denervation, spinal cord injury, and at least some conditioned reflexes. Considerable work is necessary before we fully appreciate the biological significance of respiratory plasticity, its underlying cellular/molecular and network mechanisms, and the potential to harness respiratory plasticity as a therapeutic tool.

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Prolonged stimulation for respiration by endogenous central serotonin

Cited by 207 publications

References 27 publications

Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network

Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network

Activity ofTachykinin1-ExpressingPet1Raphe Neurons Modulates the Respiratory Chemoreflex

Invited Review: Neuroplasticity in respiratory motor control

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