A5072060007- Neuroscience of respiration and sleep
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- Ion channel regulation and function
- Sleep and Wakefulness Research
- Epilepsy research and treatment
- Heart Rate Variability and Autonomic Control
- Nitric Oxide and Endothelin Effects
- Neonatal Respiratory Health Research
- Restraint-Related Deaths
- Photoreceptor and optogenetics research
- Neonatal and fetal brain pathology
- Traumatic Brain Injury and Neurovascular Disturbances
- EEG and Brain-Computer Interfaces
- Regulation of Appetite and Obesity
- Cardiac Arrest and Resuscitation
- Respiratory Support and Mechanisms
- Obstructive Sleep Apnea Research
- Cardiovascular Health and Risk Factors
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- High Altitude and Hypoxia
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiac electrophysiology and arrhythmias
- Genetics and Neurodevelopmental Disorders
University of Virginia
2014-2023
University of Virginia Health System
2021-2023
University of Connecticut
2010-2017
Universidade de São Paulo
2013-2014
Wright State University
2009
Central chemoreception is the mechanism by which CO(2)/pH sensors regulate breathing in response to tissue pH changes. There compelling evidence that pH-sensitive neurons retrotrapezoid nucleus (RTN) are important chemoreceptors. Evidence also indicates CO(2)/H(+)-evoked adenosine 5'-triphosphate (ATP) release RTN, from astrocytes, contributes chemoreception. However, mechanism(s) RTN astrocytes sense unknown and their contribution remains controversial. Here, we use brain slice preparation...
Central chemoreception is the mechanism by which brain regulates breathing in response to changes tissue CO(2)H+. A brainstem region called retrotrapezoid nucleus (RTN) contains a population of CO2/H+-sensitive neurons that appears function as an important chemoreceptor. Evidence also indicates CO2-evoked ATP release from RTN astrocytes modulates activity neurons; however, extent purinergic signalling contributes not clear and mechanism(s) underlying CO2/H+-evoked fully elucidated. The goals...
Current understanding of the contribution C1 neurons to blood pressure (BP) regulation derives predominantly from experiments performed in anesthetized animals or reduced ex vivo preparations. Here, we use ArchaerhodopsinT3.0 (ArchT) loss-of-function optogenetics explore BP by intact, unanesthetized rats. Using a lentivirus that expresses ArchT under Phox2b-activated promoter PRSx8 (PRSx8-ArchT), ∼65% transduced were (balance retrotrapezoid nucleus, RTN). Other rats received CaMKII-ArchT3.0...
Cerebral blood flow is highly sensitive to changes in CO2/H+ where an increase causes vasodilation and increased flow. Tissue also functions as the main stimulus for breathing by activating chemosensitive neurons that control respiratory output. Considering CO2/H+-induced would accelerate removal of potentially counteract drive breathe, we hypothesize brain regions have adapted a means preventing vascular CO2/H+-reactivity. Here, show rat purinergic signaling, possibly through P2Y2/4...
Objective Sudden unexpected death in epilepsy (SUDEP) is an unpredictable and devastating comorbidity of that believed to be due cardiorespiratory failure immediately after generalized convulsive seizures. Methods We performed monitoring seizure‐induced mice carrying either a p.Arg1872Trp or p.Asn1768Asp mutation single Scn8a allele—mutations identified from patients who died SUDEP—and pentylenetetrazole‐treated wild‐type mice. Results The primary cause for all was apnea, as (1) apnea began...
SCN8A epileptic encephalopathy is a devastating epilepsy syndrome caused by mutant , which encodes the voltage-gated sodium channel Na V 1.6. To date, it unclear if and how inhibitory interneurons, express 1.6, influence disease pathology. Using both sexes of transgenic mouse model encephalopathy, we found that selective expression R1872W mutation in somatostatin (SST) interneurons was sufficient to convey susceptibility audiogenic seizures. Patch-clamp electrophysiology experiments revealed...
Leptin, an adipocyte-derived hormone, is suggested to participate in the central control of breathing. We hypothesized that leptin may facilitate ventilatory responses chemoreflex activation by acting on respiratory nuclei ventrolateral medulla. The baseline ventilation and CO2 were evaluated before after daily injections into retrotrapezoid nucleus/parafacial group (RTN/pFRG) for 3 days obese leptin-deficient (ob/ob) mice.
Key points Several brain regions are thought to sense changes in tissue CO 2 /H + regulate breathing (i.e. central chemoreceptors) including the nucleus of solitary tract (NTS), medullary raphe and retrotrapezoid (RTN). Mechanism(s) underlying RTN chemoreception involve direct activation neurons by H ‐mediated inhibition a resting K conductance indirect purinergic signalling, most likely from ‐sensitive astrocytes. Here, we confirm that P2 receptors stimulates cardiorespiratory activity,...
Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing response to CO 2 /H + changes. Their activity is also sensitive neuromodulatory inputs from multiple respiratory centers, and thus they serve as a key nexus of control. However, molecular mechanisms that control their susceptibility neuromodulation are unknown. Here, we show vitro vivo KCNQ channels critical determinants RTN neural activity. In particular, find pharmacological block (XE991, 10 μ m ) increased basal...
Catecholaminergic C1 cells of the rostral ventrolateral medulla (RVLM) are key determinants sympathoexcitatory response to peripheral chemoreceptor activation. Overactivation this reflex is thought contribute increased sympathetic activity and hypertension; however, molecular mechanisms linking drive hypertension remain poorly understood. We have recently determined that activation P2Y1 receptors in RVLM mimicked effects Therefore, we hypothesize regulate region. Here, determine whether...
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of amongst patients whose seizures are not adequately controlled by current therapies. Patients with SCN8A encephalopathy have an elevated risk for SUDEP. While transgenic mouse models provided insight into molecular mechanisms etiology, our understanding seizure-induced has been hampered inability to reliably trigger both and these mice. Here, we demonstrate that mice harboring Scn8a allele patient-derived mutation N1768D...
Nitric oxide (NO) is an important signaling molecule that regulates numerous physiological processes, including activity of respiratory motoneurons. However, molecular mechanism(s) underlying NO modulation motoneurons remain obscure. Here, we used a combination in vivo and vitro recording techniques to examine the hypoglossal motor nucleus (HMN). Microperfusion diethylamine (DEA; donor) into HMN anesthetized adult rats increased genioglossus muscle activity. In brain slice, whole cell...
SCN8A epileptic encephalopathy is caused predominantly by de novo gain-of-function mutations in the voltage-gated sodium channel Na
Sudden unexpected death in epilepsy (SUDEP) accounts for the deaths of 8-17% patients with epilepsy. Although mechanisms SUDEP are unknown, one proposed mechanism is abnormal control heart by autonomic nervous system (ANS). Our objective was to determine whether broad changes ictal rate experienced mouse models (1) due ANS and (2) contribute seizure-induced death. Seizures were induced electrical stimulation hippocampus a carrying human SCN8A encephalopathy mutation p.Asn1768Asp (N1768D;...
Sudden unexpected death in epilepsy (SUDEP) accounts for the deaths of 8–17% patients with epilepsy. Although mechanisms SUDEP are essentially unknown, one proposed mechanism is respiratory arrest initiated by a convulsive seizure. In mice, we have previously observed that extended apnea occurs during tonic phase seizures. often survived, seizures became fatal when breathing did not immediately recover postictally. We also found muscles were tonically contracted apnea, suggesting muscle...
Evidence suggests that, in addition to regulate energy homeostasis, leptin also contributes the CNS control of breathing response changes CO 2 /H + (i.e., central chemoreception). However, cellular targets leptin‐dependent drive breathe have not been elucidated. Here, we tested effects on hypercapnic ventilatory deficient mice (ob/ob: 42±2 g) vivo , and ‐responsiveness RTN neurons astrocytes brain slices isolated from rat pups (P7–12). We found that 3‐ day unilateral injections (1 μg/100 nl,...