Serotonin Neurons and Central Respiratory Chemoreception

Teran, Frida A.; Massey, Cory A.; Richerson, George B.

doi:10.1016/b978-0-444-63274-6.00011-4

Cited by 76 publications

(63 citation statements)

References 112 publications

(177 reference statements)

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“…In 5-HT neurons, the change in conductance of TASK channels is small over the pH range studied here (7.4-7.15) (Teran et al 2014;Washburn et al 2002), so it would not be expected to cause the large change in firing frequency seen in 5-HT neurons over this pH range. It is also unlikely that such a small shift in TASK conductance caused by acidosis would be enough to cause the firing frequency of these neurons to increase to 300% of baseline, when motor neurons express higher levels of TASK channels but are not strongly depolarized by acidosis (Talley et al 2001;Washburn et al 2002).…”

Section: Discussionmentioning

confidence: 95%

“…The firing frequency responses of 5-HT neurons to acidosis were neither exaggerated nor blunted in isoflurane, when the hyperpolarizing influences were compensated. For these and other reasons, it is unlikely that TASK channels are the mediators of 5-HT neuron chemosensitivity (Corcoran et al 2009;Teran et al 2014).…”

Section: Discussionmentioning

confidence: 98%

“…A lack of consistent chemosensitivity in vivo has led some to conclude that 5-HT neurons are not CRCs (Depuy et al 2011;Guyenet et al 2005; Richerson et al 2005). These contradictory data constitute the major remaining argument against the hypothesis that 5-HT neurons in the medulla are CRCs (Teran et al 2014). One potential confounding factor is that in the two studies that failed to show 5-HT neuron chemosensitivity animals were anesthetized with halothane or isoflurane (Depuy et al 2011;Mulkey et al 2004).…”

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confidence: 97%

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Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂chemosensitivity

Massey

Iceman

Johansen

et al. 2015

Journal of Neurophysiology

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Serotonin (5-hydroxytryptamine, 5-HT) neurons from the mouse and rat rostral medulla are stimulated by increased CO2 when studied in culture or brain slices. However, the response of 5-HT neurons has been variable when animals are exposed to hypercapnia in vivo. Here we examined whether halogenated inhalational anesthetics, which activate TWIK-related acid-sensitive K(+) (TASK) channels, could mask an effect of CO2 on 5-HT neurons. During in vivo plethysmography in mice, isoflurane (1%) markedly reduced the hypercapnic ventilatory response (HCVR) by 78-96% depending upon mouse strain and ambient temperature. In a perfused rat brain stem preparation, isoflurane (1%) reduced or silenced spontaneous firing of medullary 5-HT neurons in situ and abolished their responses to elevated perfusate Pco2. In dissociated cell cultures, isoflurane (1%) hyperpolarized 5-HT neurons by 6.52 ± 3.94 mV and inhibited spontaneous firing. A subsequent decrease in pH from 7.4 to 7.2 depolarized neurons by 4.07 ± 2.10 mV, but that was insufficient to reach threshold for firing. Depolarizing current restored baseline firing and the firing frequency response to acidosis, indicating that isoflurane did not block the underlying mechanisms mediating chemosensitivity. These results demonstrate that isoflurane masks 5-HT neuron chemosensitivity in vitro and in situ and markedly decreases the HCVR in vivo. The use of this class of anesthetic has a particularly potent inhibitory effect on chemosensitivity of 5-HT neurons.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 97%

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Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂chemosensitivity

Massey

Iceman

Johansen

et al. 2015

Journal of Neurophysiology

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“…Central neurons using 5-HT as their neurotransmitter play a major role in regulating hemodynamic (Watts et al, 2012) and chemosensory/ventilatory (Teran et al, 2014) control systems via many 5-HT receptor subtypes. Disorders within serotonergic pathways (e.g., altered 5-HT release and reuptake; receptor down-regulation) are implicated in the etiology of disorders of cardiovascular (Watts et al, 2012) and ventilatory (Hilaire et al, 2010) systems in humans, the interplay between these vital systems (Szczepanska-Sadowska et al, 2010) and in cardiorespiratory dysfunction in humans with sleep apnea Fenik and Veasey, 2003).…”

Section: Discussionmentioning

confidence: 99%

Effects of intracerebroventricular injections of 5-HT on systemic vascular resistances of conscious rats

Davisson

Bates

Johnson

et al. 2014

Microvascular Research

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The aims of this study were to determine (i) the effects of intracerebroventricular (i.c.v.) injections of 5-hydroxytryptamine (5-HT, 10 µg) on mean arterial blood pressure (MAP), heart rate (HR) and mesenteric (MR), renal (RR) and hindquarter (HQR) vascular resistances of conscious rats, (ii) the central 5-HT receptor subtype which mediates these effects, and (iii) the role of nitric oxide (NO) in the expression of these responses. The i.c.v. injection of 5-HT had minor effects on MAP but produced a decrease in HR (−18 ± 4%), which lasted for 20 min. The i.c.v. injection of 5-HT elicited marked increases in MR (+50 ± 7%) and reductions in HQR (−31 ± 3%). These responses occurred promptly and lasted for 25–35 min. 5-HT also produced a transient decrease in RR (−26 ± 8% at 10 min). All of these responses were prevented by the prior i.c.v. injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (10 µg). The intravenous injection of the NO synthesis inhibitor, L-NAME (25 µmol/kg), produced a sustained pressor response, bradycardia and increases in MR, RR and HQR. Subsequent i.c.v. injection of 5-HT produced a minor pressor response (+7 ± 2%), bradycardia (−18 ± 3%), an increase in MR (+52 ± 8%) but no decreases in RR or HQR. This study demonstrates that i.c.v. 5-HT differentially affects peripheral vascular resistances by activation of central 5-HT1/5-HT2-receptors. It appears that L-NAME did not interfere with the central actions of 5-HT as it did not prevent the 5-HT-induced bradycardia or mesenteric vasoconstriction. Since the 5-HT-induced falls in RR and HQR were abolished by L-NAME, it is possible that these responses are mediated by an active neurogenic process involving the release of NO within the vasculature.

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“…5-HT neurons found in the medullary raphe act as central chemoreceptors that regulate PCO 2 and pH and project to key respiratory neurons throughout the brainstem to stimulate breathing 69. Lmx1b f/f/p mice, which lack >99% of 5-HT neurons in the central nervous system by genetic deletion in utero , exhibit high rates of apnoea and death during the early postnatal period along with defects in arousal to an increase in ambient CO 2 during sleep 40 70.…”

Section: Pathophysiologymentioning

confidence: 99%

Sudden unexpected death in epilepsy: basic mechanisms and clinical implications for prevention

Dlouhy

Gehlbach

Richerson

2015

J Neurol Neurosurg Psychiatry

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Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with intractable epilepsy. The substantial lifetime risk of SUDEP and the lack of a clear pathophysiological connection between epilepsy itself and sudden death have fuelled increased attention to this phenomenon. Understanding the mechanisms underlying SUDEP is paramount to developing preventative strategies. In this review, we discuss SUDEP population studies, case-control studies, witnessed and monitored cases, as well as human seizure cardiorespiratory findings related to SUDEP, and SUDEP animal models. We integrate these data to suggest the most probable mechanisms underlying SUDEP. Understanding the modifiable risk factors and pathophysiology allows us to discuss potential preventative strategies.

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Serotonin Neurons and Central Respiratory Chemoreception

Cited by 76 publications

References 112 publications

Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂chemosensitivity

Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂chemosensitivity

Effects of intracerebroventricular injections of 5-HT on systemic vascular resistances of conscious rats

Sudden unexpected death in epilepsy: basic mechanisms and clinical implications for prevention

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Serotonin Neurons and Central Respiratory Chemoreception

Cited by 76 publications

References 112 publications

Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO2chemosensitivity

Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO2chemosensitivity

Effects of intracerebroventricular injections of 5-HT on systemic vascular resistances of conscious rats

Sudden unexpected death in epilepsy: basic mechanisms and clinical implications for prevention

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Product

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Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂chemosensitivity

Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂chemosensitivity