Daniel K. Mulkey
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View article: Developmental progression of respiratory dysfunction in a mouse model of Dravet syndrome
Developmental progression of respiratory dysfunction in a mouse model of Dravet syndrome Open
Dravet syndrome (DS) is an early-onset epilepsy caused by loss-of-function mutations in the SCN1A gene, which encodes Nav1.1 channels that preferentially regulate activity of inhibitory neurons early in development. DS is associated with a…
View article: Oxytocinergic signalling in the respiratory parafacial region increases the activity of chemosensitive neurons and respiratory output
Oxytocinergic signalling in the respiratory parafacial region increases the activity of chemosensitive neurons and respiratory output Open
The retrotrapezoid nucleus, located in the parafacial medullary region (RTN/pFRG), is crucial for respiratory activity and central chemoreception. Recent evidence suggests that neuromodulation, including peptidergic signalling, can influen…
View article: Parvalbumin-expressing neurons in the ventral medulla are active during wakefulness and promote NREM sleep
Parvalbumin-expressing neurons in the ventral medulla are active during wakefulness and promote NREM sleep Open
A longstanding hypothesis contends that sleep is promoted by sleep–active inhibitory neurons that suppress arousal centers. Sleep may also be facilitated by mechanisms active during wakefulness; however, evidence for wake–active sleep-prom…
View article: Update on vascular control of central chemoreceptors
Update on vascular control of central chemoreceptors Open
At least four mechanisms have been proposed to elucidate how neurons in the retrotrapezoid (RTN) region sense changes in CO 2 /H + to regulate breathing (i.e., function as respiratory chemosensors). These mechanisms include: (1) intrinsic …
View article: Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline
Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline Open
BACKGROUND: Respiratory dysfunction is a common complication of stroke, with an incidence of over 60%. Despite the high prevalence of stroke-induced respiratory dysfunction, how disordered breathing influences recovery and cognitive outcom…
View article: Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt–Hopkins syndrome
Promyelinating drugs promote functional recovery in an autism spectrum disorder mouse model of Pitt–Hopkins syndrome Open
Pitt–Hopkins syndrome is an autism spectrum disorder caused by autosomal dominant mutations in the human transcription factor 4 gene (TCF4). One pathobiological process caused by murine Tcf4 mutation is a cell autonomous reduction in oligo…
View article: Perspectives on the basis of seizure-induced respiratory dysfunction
Perspectives on the basis of seizure-induced respiratory dysfunction Open
Epilepsy is an umbrella term used to define a wide variety of seizure disorders and sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in epilepsy. Although some SUDEP risk factors have been identified, it remains la…
View article: Histamine/H1 receptor signaling in the parafacial region increases activity of chemosensitive neurons and respiratory activity in rats
Histamine/H1 receptor signaling in the parafacial region increases activity of chemosensitive neurons and respiratory activity in rats Open
Histamine/H1 receptor signaling activates retrotrapezoid (RTN) neurons under control conditions and to a lesser extent in the presence of serotonin. These results suggest that RTN neurons have a limited capacity to respond to simultaneous …
View article: Clemastine fumarate enhances myelination and promotes functional recovery in a syndromic ASD mouse model of Pitt-Hopkins Syndrome
Clemastine fumarate enhances myelination and promotes functional recovery in a syndromic ASD mouse model of Pitt-Hopkins Syndrome Open
Pitt-Hopkins syndrome (PTHS) is an autism spectrum disorder (ASD) caused by autosomal dominant mutations in the Transcription Factor 4 gene ( TCF4 ). One pathobiological process caused by Tcf4 mutation is a cell autonomous reduction in oli…
View article: 5‐HT7 receptors expressed in the mouse parafacial region are not required for respiratory chemosensitivity
5‐HT7 receptors expressed in the mouse parafacial region are not required for respiratory chemosensitivity Open
A brainstem homeostatic system senses CO 2 /H + to regulate ventilation, blood gases and acid–base balance. Neurons of the retrotrapezoid nucleus (RTN) and medullary raphe are both implicated in this mechanism as respiratory chemosensors, …
View article: Somatostatin-expressing parafacial neurons are CO2/H+ sensitive and regulate baseline breathing
Somatostatin-expressing parafacial neurons are CO2/H+ sensitive and regulate baseline breathing Open
Glutamatergic neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating breathing in response to tissue CO 2 /H + . The RTN and greater parafacial region may also function as a chemosensing network co…
View article: The retrotrapezoid nucleus and the neuromodulation of breathing
The retrotrapezoid nucleus and the neuromodulation of breathing Open
Breathing is regulated by a host of arousal and sleep-wake state-dependent neuromodulators to maintain respiratory homeostasis. Modulators such as acetylcholine, norepinephrine, histamine, serotonin (5-HT), adenosine triphosphate (ATP), su…
View article: Vascular control of the CO2/H+-dependent drive to breathe
Vascular control of the CO2/H+-dependent drive to breathe Open
Respiratory chemoreceptors regulate breathing in response to changes in tissue CO 2 /H + . Blood flow is a fundamental determinant of tissue CO 2 /H + , yet little is known regarding how regulation of vascular tone in chemoreceptor regions…
View article: K<sub>ir</sub>5.<scp>1‐dependent CO<sub>2</sub></scp>/H<sup>+</sup>‐sensitive currents contribute to astrocyte heterogeneity across brain regions
K<sub>ir</sub>5.<span>1‐dependent CO<sub>2</sub></span>/H<sup>+</sup>‐sensitive currents contribute to astrocyte heterogeneity across brain regions Open
Astrocyte heterogeneity is an emerging concept in which astrocytes within or between brain regions show variable morphological and/or gene expression profiles that presumably reflect different functional roles. Recent evidence indicates th…
View article: Volatile Anesthetics Activate a Leak Sodium Conductance in Retrotrapezoid Nucleus Neurons to Maintain Breathing during Anesthesia in Mice
Volatile Anesthetics Activate a Leak Sodium Conductance in Retrotrapezoid Nucleus Neurons to Maintain Breathing during Anesthesia in Mice Open
Background Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isofluran…
View article: Isoflurane inhibits a Kir4.1/5.1-like conductance in neonatal rat brainstem astrocytes and recombinant Kir4.1/5.1 channels in a heterologous expression system
Isoflurane inhibits a Kir4.1/5.1-like conductance in neonatal rat brainstem astrocytes and recombinant Kir4.1/5.1 channels in a heterologous expression system Open
An unwanted side effect of isoflurane anesthesia is suppression of breathing. Despite this clinical significance, effects of isoflurane on cellular and molecular elements of respiratory control are not well understood. Here, we show that i…
View article: Faculty Opinions recommendation of One bout of neonatal inflammation impairs adult respiratory motor plasticity in male and female rats.
Faculty Opinions recommendation of One bout of neonatal inflammation impairs adult respiratory motor plasticity in male and female rats. Open
Neonatal inflammation is common and has lasting consequences for adult health. We investigated the lasting effects of a single bout of neonatal inflammation on adult respiratory control in the form of respiratory motor plasticity induced b…
View article: Disordered breathing in a mouse model of Dravet syndrome
Disordered breathing in a mouse model of Dravet syndrome Open
Dravet syndrome (DS) is a form of epilepsy with a high incidence of sudden unexpected death in epilepsy (SUDEP). Respiratory failure is a leading cause of SUDEP, and DS patients’ frequently exhibit disordered breathing. Despite this, mecha…
View article: Author response: Disordered breathing in a mouse model of Dravet syndrome
Author response: Disordered breathing in a mouse model of Dravet syndrome Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Dravet syndrome (DS) is a form of epilepsy…
View article: Cholinergic neurons in the pedunculopontine tegmental nucleus modulate breathing in rats by direct projections to the retrotrapezoid nucleus
Cholinergic neurons in the pedunculopontine tegmental nucleus modulate breathing in rats by direct projections to the retrotrapezoid nucleus Open
Key points Cholinergic projections from the pedunculopontine tegmental nucleus (PPTg) to the retrotrapezoid nucleus (RTN) are considered to be important for sleep–wake state‐dependent control of breathing. The RTN also receives cholinergic…
View article: Disordered breathing in a mouse model of Dravet syndrome
Disordered breathing in a mouse model of Dravet syndrome Open
Dravet syndrome (DS) is a form of epilepsy with a high incidence of sudden unexpected death in epilepsy (SUDEP). Respiratory failure is a leading cause of SUDEP, and DS patients’ frequently exhibit disordered breathing. Despite this, mecha…
View article: Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus
Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus Open
A subset of neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating depth and frequency of breathing in response to changes in tissue CO 2 /H + . The activity of chemosensitive RTN neurons is also s…