A5041693134- Neuroscience of respiration and sleep
- Heart Rate Variability and Autonomic Control
- Sleep and Wakefulness Research
- Obstructive Sleep Apnea Research
- Neuroendocrine regulation and behavior
- Neuroscience and Neuropharmacology Research
- Circadian rhythm and melatonin
- Neonatal Respiratory Health Research
- Lipid Membrane Structure and Behavior
- Nitric Oxide and Endothelin Effects
- High Altitude and Hypoxia
- Sphingolipid Metabolism and Signaling
- Eicosanoids and Hypertension Pharmacology
- Spinal Cord Injury Research
- Regulation of Appetite and Obesity
- Stress Responses and Cortisol
- Respiratory Support and Mechanisms
- Cardiovascular and Diving-Related Complications
- Advanced Chemical Sensor Technologies
- Neuropeptides and Animal Physiology
- Anesthesia and Neurotoxicity Research
- Neurological disorders and treatments
- Blood Pressure and Hypertension Studies
- Cellular transport and secretion
- Infant Health and Development
University of Virginia
2017-2025
Universidade de São Paulo
2016-2019
Universidade de Ribeirão Preto
2014
Respiratory chemoreceptor activity encoding arterial P co 2 and o is a critical determinant of ventilation. Currently, the relative importance several putative mechanisms for maintaining eupneic breathing respiratory homeostasis debated. Transcriptomic anatomic evidence suggests that bombesin-related peptide Neuromedin-B ( Nmb ) expression identifies neurons in retrotrapezoid nucleus (RTN) mediate hypercapnic ventilatory response, but functional support missing. In this study, we generated...
Key points The retrotrapezoid nucleus (RTN) drives breathing proportionally to brain but its role during various states of vigilance needs clarification. Under normoxia, RTN lesions increased the arterial set‐point, lowered set‐point and reduced alveolar ventilation relative CO 2 production. Tidal volume was frequency a comparable degree wake, slow‐wave sleep REM sleep. did not produce apnoeas or disordered in rats virtually eliminated central respiratory chemoreflex (CRC) while preserving...
Hemorrhage initially triggers a rise in sympathetic nerve activity (SNA) that maintains blood pressure (BP); however, SNA is suppressed following severe loss causing hypotension. We hypothesized adrenergic C1 neurons the rostral ventrolateral medulla (C1RVLM) drive increase during compensated hemorrhage, and reduction C1RVLM contributes to hypotension decompensated hemorrhage. Using fiber photometry, we demonstrate increases hemorrhage falls at onset of optogenetics combined with direct...
Collectively, the retrotrapezoid nucleus (RTN) and adjacent C1 neurons regulate breathing, circulation state of vigilance, but previous methods to manipulate activity these have been insufficiently selective parse out their relative roles. We hypothesize that RTN distinct aspects breathing (e.g., frequency, amplitude, active expiration, sighing) differ in ability produce arousal from sleep. Here we use optogenetics a combination viral vectors adult male female Th -Cre rats transduce...
Sphingosine-1-phosphate (S1P) receptor modulator (SRM) drugs suppress immune system function by disrupting lymphocyte trafficking, but SRMs are broadly immunosuppressive with on-target liabilities. Another strategy to modulate the is block S1P transport. This study tests hypothesis that blockers of transport (STBs) mediated Spinster homologue 2 (Spns2) approximate efficacy without their adverse events. We have discovered and optimized STBs enable investigations biology determine whether a...
The combination of hypoxia and hypercapnia during sleep produces arousal, which helps restore breathing normalizes blood gases. Hypercapnia produce arousal in mammals by activating central (pH-sensitive) peripheral (primarily O 2 -sensitive) chemoreceptors. relevant chemoreceptors the neuronal circuits responsible for are largely unknown. Here we examined contribution two lower brainstem nuclei that could be implicated CO hypoxia-induced arousal: retrotrapezoid nucleus (RTN), a -responsive...
Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics WAG/Rij rat, an established rodent model of epilepsy, we demonstrate are highly sensitive arterial carbon dioxide, suggesting pH. Moreover, consistently activated neurons within...
In mammals, the pontine noradrenergic system influences nearly every aspect of central nervous function. A subpopulation neurons, called A5, are thought to be important in cardiovascular response physical stressors, yet their function is poorly defined. We hypothesized that activation A5 neurons drives a sympathetically mediated increase blood pressure (BP). To test this hypothesis, we conducted comprehensive assessment effects chemogenetic stimulation male and female adult rats using...
Metabolism regulates neuronal activity and modulates the occurrence of epileptic seizures. Here, using two rodent models absence epilepsy, we show that hypoglycaemia increases spike-wave We then selectively disrupting glycolysis in thalamus, a structure implicated is sufficient to increase propose activation thalamic AMP-activated protein kinase, sensor cellular energetic stress potentiator metabotropic GABAB-receptor function, significant driver hypoglycaemia-induced kinase augments...
What is the central question of this study? The arterial baroreflex regulates pressure within a narrow range variation. After sino-aortic denervation (SAD), rats show large increase in variability, but mean levels remain similar to those control rats. Considering that breathing influences pressure, is: what extent does SAD cause changes breathing? main finding and its importance? Removal baroreceptors produced rats, marked by reduction respiratory frequency, not hypertension. These findings...
The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control, serving as significant source of synaptic input to spinal cord. Experimental studies have shown that gene expression individual VLM neurons predictive their function. However, molecular cellular organization has remained uncertain. This study aimed create comprehensive dataset cells using single-cell RNA sequencing male female mice. was enriched with targeted spinally-projecting...
The homeostatic regulation of pulmonary ventilation, and ultimately arterial PCO
New Findings What is the central question of this study? Sino‐aortic denervated (SAD) rats present normal levels sympathetic activity and mean arterial pressure. However, neural mechanisms regulating in absence baroreceptors remain unclear. Considering that respiration modulates activity, we hypothesize changes respiratory network contribute to keep outflow range after removal baroreceptors. main finding its importance? Despite longer inspiration observed SAD rats, respiratory–sympathetic...
Abstract S1P (sphingosine 1-phosphate) receptor modulator (SRM) drugs interfere with lymphocyte trafficking by downregulating receptors. While the immunosuppressive activity of SRM has proved useful in treating autoimmune diseases such as multiple sclerosis, that drug class is beset on-target liabilities initial dose bradycardia. The binds to cell surface receptors provided transporters. Mice born deficient one these, spinster homolog 2 (Spns2), are lymphocytopenic and have low lymph...
Central respiratory chemoreceptors regulate breathing homeostasis in relation to arterial pH/PCO 2 . Neurons located the retrotrapezoid nucleus (RTN) are considered function as central and/or be part of neural network that drives chemoreflex. RTN neurons sensitive changes pH vitro under synaptic blockade and anesthetized preparations with artificial ventilation. However, there is limited information about their activity vivo non-anesthetized conditions. Recent studies have shown...
Catecholaminergic neurons in the ventrolateral medulla (VLM) regulate many important aspects of physiology, including sympathetic control blood pressure, glucose homeostasis, immune function, and neuroendocrine responses to inflammation stress. Previous studies have parsed catecholaminergic VLM into distinct sub-populations based on neurochemical content, connectivity, response activation autonomic reflexes. However, there is no consensus for molecular organization neurons. In this study, we...
Abstract The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control. It also serves as significant source of synaptic input to spinal cord. Experimental studies have shown that gene expression individual VLM neurons predictive their function. However, organizing principles remained uncertain. This study aimed create comprehensive dataset cells using single-cell RNA sequencing. was enriched with targeted sequencing spinally-projecting...
New Findings What is the central question of this study? After sino‐aortic denervation (SAD), rats present normal levels mean arterial pressure (MAP), high MAP variability and changes in breathing. However, mechanisms involved SAD‐induced respiratory their impact on modulation sympathetic activity remain unclear. Herein, we characterized firing frequency medullary neurons after SAD. main finding its importance? Sino‐aortic denervation‐induced prolonged inspiration was associated with a...