A5029708027- Neuroscience of respiration and sleep
- Heart Rate Variability and Autonomic Control
- Neuroendocrine regulation and behavior
- Sleep and Wakefulness Research
- Blood Pressure and Hypertension Studies
- Stress Responses and Cortisol
- High Altitude and Hypoxia
- Circadian rhythm and melatonin
- Renin-Angiotensin System Studies
- Cardiovascular Syncope and Autonomic Disorders
- Infant Health and Development
- Neonatal Respiratory Health Research
- Traumatic Brain Injury and Neurovascular Disturbances
- Cardiovascular Function and Risk Factors
- Nitric Oxide and Endothelin Effects
- Neuropeptides and Animal Physiology
- Respiratory Support and Mechanisms
- Cardiovascular and exercise physiology
- Receptor Mechanisms and Signaling
- Cardiovascular Health and Disease Prevention
- Cerebrovascular and Carotid Artery Diseases
- Biochemical effects in animals
- Obstructive Sleep Apnea Research
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Cardiac Imaging and Diagnostics
University of Auckland
2016-2025
Health Research Council of New Zealand
2023
National Heart Foundation of New Zealand
2023
University of Bristol
2013-2022
The Centre for Health (New Zealand)
2022
University Hospitals Bristol NHS Foundation Trust
2012-2021
Universidade de São Paulo
2007-2021
NIHR Bristol Cardiovascular Biomedical Research Unit
2008-2017
North Bristol NHS Trust
2017
Southmead Hospital
2017
Mammalian central pattern generators (CPGs) producing rhythmic movements exhibit extremely robust and flexible behavior. Network architectures that enable these features are not well understood. Here we studied organization of the brain stem respiratory CPG. By sequential rostral to caudal transections through pontine-medullary network within an in situ perfused rat stem–spinal cord preparation, showed dynamics reorganized new rhythmogenic mechanisms emerged. The normal three-phase rhythm...
Abstract Astrocytes produce and release L -lactate as a potential source of energy for neurons. Here we present evidence that -lactate, independently its caloric value, serves an astrocytic signalling molecule in the locus coeruleus (LC). The LC is principal norepinephrine to frontal brain thus one most influential modulatory centers brain. Optogenetically activated astrocytes which excites neurons triggers norepinephrine. Exogenous within physiologically relevant concentration range mimics...
The peripheral chemoreflex is known to be enhanced in individuals with hypertension. In pre-hypertensive (PH) and adult spontaneously hypertensive rats (SHRs) carotid body type I (glomus) cells exhibit hypersensitivity chemosensory stimuli elevated sympathoexcitatory responses chemoreceptor stimulation. Herein, we eliminated inputs both PH-SHRs SHRs test the hypothesis that heightened activity contributes development maintenance of sinus nerves were surgically denervated under general...
Abstract Astrocytes provide neurons with essential metabolic and structural support, modulate neuronal circuit activity may also function as versatile surveyors of brain milieu, tuned to sense conditions potential insufficiency. Here we show that astrocytes detect falling cerebral perfusion pressure activate CNS autonomic sympathetic control circuits increase systemic arterial blood heart rate the purpose maintaining flow oxygen delivery. Studies conducted in experimental animals (laboratory...
Chronic intermittent hypoxia (CIH) in rats produces changes the central regulation of cardiovascular and respiratory systems by unknown mechanisms. We hypothesized that CIH (6% O(2) for 40 s, every 9 min, 8 h day(-1)) 10 days alters modulation sympathetic activity. After CIH, awake (n = 14) exhibited higher levels mean arterial pressure than controls (101 +/- 3 versus 89 mmHg, n 15, P < 0.01). Recordings phrenic, thoracic sympathetic, cervical vagus abdominal nerves were performed situ...
Sympathetic nerve activity (SNA) is elevated in established hypertension. We tested the hypothesis that SNA neonate and juvenile spontaneously hypertensive (SH) rats prior to development of hypertension, this may be due augmented respiratory-sympathetic coupling. Using working heart-brainstem preparation, perfusion pressure, phrenic thoracic (T8) were recorded male SH normotensive Wistar-Kyoto (WKY) at three ages: neonates (postnatal day 9-16), 3 weeks old 5 old. Perfusion pressure was...
We studied respiratory neural activity generated during expiration. Motoneuronal was recorded simultaneously from abdominal (AbN), phrenic (PN), hypoglossal (HN) and central vagus nerves neonatal juvenile rats in situ . During eupnoeic activity, low‐amplitude post‐inspiratory (post‐I) discharge only present AbN motor outflow. Expression of late‐expiratory (late‐E) preceding PN bursts, occurred hypercapnia. Biphasic expiratory (biphasic‐E) with pre‐inspiratory (pre‐I) post‐I discharges...
Peripheral immune activation can have profound physiological and behavioral effects including induction of fever sickness behavior. One mechanism through which or immunomodulation may affect physiology behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We found that peripheral with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset neurons in interfascicular part dorsal raphe nucleus (DRI)...
Rett syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked gene that encodes transcription factor methyl-CpG-binding protein 2 (MeCP2). A major debilitating phenotype affected females frequent apneas, and heterozygous Mecp2 -deficient female mice mimic human respiratory disorder. GABA defects have been demonstrated brainstem of Mecp2-deficient mice. Here, using intact network, we show apnea RTT characterized excessive excitatory activity expiratory cranial spinal...
Phox2b-expressing neurons of the retrotrapezoid nucleus (RTN), located in ventrolateral brainstem, are sensitive to changes PCO 2 /pH, have excitatory projections central respiratory rhythm/pattern generator, and their activation enhances drive. Using vivo (conscious anesthetized rats) situ (arterially perfused rat brainstem–spinal cord preparations) models, we evaluated functional significance this neuronal population for both resting activity CO -evoked responses by reversibly inhibiting...
We conducted a theoretical study of the physiological significance respiratory sinus arrhythmia (RSA), phenomenon used as an index cardiac vagal tone and wellbeing, whereby heart rate (HR) increases during inspiration decreases expiration. first tested hypothesis that RSA improves gas exchange efficiency but found although improved with slow deep breathing increased mean rate, this was unrelated to RSA. then formulated new hypothesis: minimizes work done by while maintaining levels arterial...
Animal and human data indicate pathological afferent signaling emanating from the carotid body that drives sympathetically mediated elevations in blood pressure conditions of hypertension. This first-in-man, proof-of-principle study tested safety feasibility unilateral resection 15 patients with drug-resistant The procedure proved to be safe feasible. Overall, no change was found. However, 8 showed significant reductions ambulatory coinciding decreases sympathetic activity. may a novel...
Key points In addition to reductions in respiratory rate, opioids also cause aspiration and difficulty swallowing, indicating impairment of the upper airways. The Kölliker–Fuse (KF) maintains airway patency a normal pattern. this study, activation μ opioid receptors KF reduced frequency tidal volume anaesthetized rats. Nerve recordings an situ preparation showed that eliminated post‐inspiration phase cycle. brain slices, agonists hyperpolarized distinct population (61%) neurons by inwardly...