A5069626014- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Connexins and lens biology
- Nitric Oxide and Endothelin Effects
- Cardiac electrophysiology and arrhythmias
- Traumatic Brain Injury and Neurovascular Disturbances
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Mitochondrial Function and Pathology
- Ion Channels and Receptors
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Barrier Structure and Function Studies
- Neuroscience of respiration and sleep
- Heart Rate Variability and Autonomic Control
- Metabolomics and Mass Spectrometry Studies
- Thermoregulation and physiological responses
- Retinal Development and Disorders
- EEG and Brain-Computer Interfaces
- Neurological Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Optical Coherence Tomography Applications
- Optical Imaging and Spectroscopy Techniques
- Advanced Fluorescence Microscopy Techniques
- Planarian Biology and Electrostimulation
University of Nevada, Reno
2019-2024
University of Calgary
2012-2022
Allen Institute for Brain Science
2020
Libin Cardiovascular Institute of Alberta
2009-2019
University of Alberta
2003-2004
According to the current model of neurovascular coupling, blood flow is controlled regionally through phasic changes in activity neurons and astrocytes that signal alter arteriole diameter. Absent this model, however, how brain tonically regulated independent regional activity. This important because a large fraction required maintain basal metabolic needs. Using two-photon fluorescence imaging combined with patch-clamp acute rat slices sensory-motor cortex, we demonstrate reducing resting...
Cerebral blood flow is dynamically regulated by neurovascular coupling to meet the dynamic metabolic demands of brain. We hypothesized that TRPA1 channels in capillary endothelial cells are stimulated neuronal activity and instigate a propagating retrograde signal dilates upstream parenchymal arterioles initiate functional hyperemia. find activation beds post-arteriole transitional segments with mural cell coverage initiates signals dilate arterioles. These exhibit unique mode biphasic...
Functional hyperemia occurs when enhanced neuronal activity signals to increase local cerebral blood flow (CBF) satisfy regional energy demand. Ca
When arteries constrict to agonists, the endothelium inversely responds, attenuating initial vasomotor response. The basis of this feedback mechanism remains uncertain, although past studies suggest a key role for myoendothelial communication in signaling process. present study examined whether second messenger flux through gap junctions initiates negative-feedback response hamster retractor muscle feed arteries. We specifically hypothesized that when agonists elicit depolarization and rise...
Two-photon laser scanning microscopy has revolutionized the ability to delineate cellular and physiological function in acutely isolated tissue vivo. However, there exist barriers for many laboratories acquire two-photon microscopes. Additionally, if owned, typical systems are difficult modify rapidly evolving methodologies. A potential solution these problems is enable scientists build their own high-performance adaptable system by overcoming a resource insufficiency. Here we present...
Abstract Dynamic changes in astrocyte Ca 2+ are recognized as contributors to functional hyperemia, a critical response increased neuronal activity mediated by process known neurovascular coupling (NVC). Although the role of glutamatergic signaling this has been extensively investigated, impact behavioral state, and release behavior-associated neurotransmitters, such norepinephrine serotonin, on dynamics hyperemia have received less attention. We used two-photon imaging barrel cortex awake...
This study examined whether elevated intravascular pressure stimulates asynchronous Ca(2+) waves in cerebral arterial smooth muscle cells and if their generation contributes to myogenic tone development. The endothelium was removed from rat arteries, which were then mounted an arteriograph, pressurized (20-100 mmHg) under a variety of experimental conditions. Diameter membrane potential (V(M)) monitored using conventional techniques; wave myosin light chain (MLC(20))/MYPT1 (myosin...
In vivo two-photon scanning fluorescence imaging is a powerful technique to observe physiological processes from the millimeter micron scale in intact animal. neuroscience research, common approach install an acute cranial window and head bar explore neocortical function under anesthesia before inflammation peaks surgery. However, there are few detailed protocols for head-restrained fully awake animal of neurovascular unit during activity. This because acutely performed experiments typically...
Seizures can result in a severe hypoperfusion/hypoxic attack that causes postictal memory and behavioral impairments. However, neither changes to microvasculature nor Ca2+ key cell types controlling blood perfusion have been visualized vivo, leaving essential components of the underlying cellular mechanisms unclear. Here, we use 2-photon microvascular imaging awake mice show seizures robust vasoconstriction cortical penetrating arterioles, which temporally mirrors prolonged hypoxia. The...
The goal of this investigation was to probe intercellular conduction in skeletal muscle feed arteries and address why smooth muscle‐initiated responses fail robustly spread like their endothelial counterpart. Using computational experimental approaches, two interrelated rationales were developed explain apparent discrepancy cell‐to‐cell communication. first rationale stressed that electrical responses, if initiated, will be actively dissipated as they from along the arterial wall. Charge...
Electrical communication and its role in blood flow regulation are built on an examination of charge movement single, isolated vessels. How this process behaves broader arterial networks remains unclear. This study examined the nature electrical structures where vessel length branching were varied. Analysis began with deployment existing computational model expanded to form a variable range structures. Initial simulations revealed that focal endothelial stimulation generated responses...
Objective: Cerebral arterial networks match blood flow delivery with neural activity. Neurovascular response begins a stimulus and focal change in vessel diameter, which by themselves is inconsequential to magnitude, until they spread alter the contractile status of neighboring segments. We sought define mechanisms underlying integrated vascular behavior considered role intercellular electrical signaling this phenomenon. Approach Results: Electron microscopic histochemical analysis revealed...
We investigated the role of myoendothelial projections (MPs) in endothelial cell (EC) feedback response to smooth muscle (SMC) stimulation using mathematical modelling. A previously developed compartmental EC-SMC model is modified include MPs as subcellular compartments EC. The further extended into a 2D continuum finite element method (FEM) approach and electron microscopy images account for MP geometry. EC SMC are coupled via non-selective gap junctions (MEGJs) which located on allow...
SUMMARY Embryos of the pond snail Helisoma trivolvis express three known subtypes ciliary cells on surface embryo early in development:pedal, dorsolateral and scattered single (SSCCs). The pedal are innervated by a pair serotonergic sensory-motor neurons responsible for generating earliest whole-animal behavior, rotation within egg capsule. Previous cell culture studies unidentified revealed that serotonin(5-hydroxytryptamine; 5-HT) produces significant increase beat frequency (CBF) large...
Abstract Objective Endothelial and smooth muscle cells must communicate with one another to regulate arterial diameter. A key structure driving heterocellular communication is the endothelial projection, a thin extension that crosses internal elastic lamina ( IEL ) making contact muscle. This study sought define precise structural composition of projections in mesenteric circulation. Methods Third‐ fourth‐order arteries from hamster were prepared for electron microscopy. Electron tomographic...
Astrocytic Ca2+ fluctuations associated with functional hyperemia have typically been measured from large cellular compartments such as the soma, whole arbor and endfoot. The most prominent event is a magnitude, delayed signal that follows vasodilation. However, previous work has provided little information about spatio-temporal properties of transients or their heterogeneity. Here, using an awake, in vivo two-photon fluorescence-imaging model, we performed detailed profiling astrocytic...