University of British Columbia
MacVicar Lab
TheLab
Lab Staff
Denise Feighan, BSc.
Lab Manager
Denise has been managing and conducting experiments in the MacVicar lab for 15 years. As well as running the operations of the lab and managing the large staff, Denise is also trained in advanced experimental procedures. Her main projects include spreading depression and ischemia (oxygen/glucose deprivation) through the use of intrinsic optical imaging experiments and prepares and dye loads brain slices for 2-photon microscopy, and provides assitance and guidance with other projects.
604-822-7893
Katherine Rhodes, MA
Network & Research Coordinator
Master of Arts, Family Studies
Katherine is the Research Facilitator for the Leducq Foundation Project, and is responsible for managing the finances and networking components of the project. Before this project began, she worked as research coordinator in women's health after she completed her Master's degree in Family Studies at UBC.
604-827-5693
Fellows
Hyun Beom Choi, PhD.
PhD., Experimental Medicine
Post Doctoral Fellow, Psychiatry
I am very interested in studying the mechanisms underlying metabolic communications between neuronal and glial cells. Astrocytes are proposed to maintain brain health by providing energy substrates to neurons from their glycogen stores and from glycolysis. However, little is known about the molecular pathways responsible for metabolic coupling between different cell types in the central nervous system. Currently, I am investigating the role of astrocytes in providing an energy sustrate to neurons in an activity dependent manner.
Grant Gordon, PhD.
PhD., Neuroscience
I am interested in how astrocytes—a type of glial cell in the brain— regulate the diameter of cerebral arterioles thereby playing a pivotal role in the control of brain blood flow. To study these aspects of astrocyte physiology, we utilize two-photon laser scanning microscopy in acute brain slices of the hippocampus, cortex. Imaging techniques encompass measurements of calcium signals, cell morphology, metabolic NADH signals and performing the photolysis of caged compounds including caged-Ca2+, caged-IP3 and caged-glutamate. Two-photon photolysis of caged molecules provides us with the ability to precisely activate astrocytes alone and thus specifically examine astrocyte-mediated phenomenon without the confounding effects of exciting other cell types. We have discovered that the metabolic activity in the brain tissue is a critical factor in dictating the type of influence astrocytes induce on cerebrovascular diameter. We found that the level of oxygen in the brain could change the metabolic state of the tissue (i.e. shift the balance between more or less glycolysis in astrocytes) and cause astrocytes to induce opposite changes to vessel diameter. When oxygen levels are high, similar to when the brain is inactive, astrocyte activation induces vasoconstriction, which would decrease blood flow. When oxygen levels are low, mimicking high activity of neurons in the brain, astrocytes cause vasodilation of arterioles. In a sense, astrocytes are tuned to the level of activity and the metabolic needs of the brain and elicit corresponding changes to cerebral blood flow to match the delivery of new energy substrates from the blood to the needs of the neurons. We are currently interested in exploring these ideas with respect to the direct metabolic shuttling of energy substrates from astrocytes to neurons and with how these principles might influence astrocyte-mediated changes in synaptic strength.
Huili Han, PhD.
Clare Howarth, PhD.
PhD., Neuroscience
MSc. Physics
Current Project: The role of astrocytes in the brain vascular response to neural activity
During my PhD I studied the control of the energy supply to the brain, both experimentally and theoretically. I discovered a new mechanism for the control of brain blood flow at the capillary level (Nature 443, 700) and I produced the first energy budget for an area of brain tissue that is based on the measured electrical properties of its cells. My research goals are to characterise in detail the cellular mechanisms by which neuronal activity regulates brain energy supply. This knowledge is essential to understand normal brain function, functional imaging techniques, and what occurs when the brain energy supply is cut off in disorders such as stroke.
It is critical for the maintenance of normal brain function that cerebral blood flow (CBF) is matched to neuronal metabolic demands. Neuronal activity leads to an increase in blood flow to the active area, and it is this increase which results in the signals necessary for functional imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). However, the mechanisms regulating CBF are only poorly understood.
The increase in blood flow results partly from neuron-arteriole signaling via a glutamate – NMDA receptor – NO – cGMP pathway. However astrocytes also regulate the blood flow through brain arterioles, as a result of astrocytic [Ca2+]i elevations which are evoked by neural activity. It has previously been observed that astrocyte [Ca2+]i elevations can lead to vasoconstriction or dilation. The mechanisms underlying these opposing effects are poorly understood, but they may reflect the release of different signalling molecules, such as 20-HETE and prostaglandins (PGE2) which lead to either vasodilation or constriction. My current project is studying the role of astrocytes in the brain vascular response to neural activity. By monitoring arteriole diameter while uncaging Ca2+ in astrocyte endfeet in hippocampal slices, I will investigate the role of astrocytes in the regulation of cerebral blood flow and compare their role with that of neuron–arteriole signalling.
Janelle Pakan, PhD.
Students
Ravi Rungta
MSc in Progress, Neuroscience
BSc.,Pshysiology
My area of research interest is synaptic and non-synaptic control of neuronal excitability. My projects include investigating a synaptic role for pannexin hemichannels, which our lab has shown opens during both stroke and epilepsy. I am also looking into mechanisms for the uptake and release of adenosine, which inhibits transmitter release via A1 receptors.
Jingfei Zhang
PhD.in Progress, Neuroscience
BSc.
Chronic activation of microglia is thought to be mediated in several pathological process. Microglias can be activated by harmful reagent such as lipopolysccharide (LPS) and beta amyloid. The release of cytokines from activated microglia are potential to generate synaptic disruption and neurodegeneration, leading to sickness behavior, memory deficits, and cognitive disfunctions.
Currently, I am in the process of doing field recording on hippocampal slices to study the mechanism of LPS induced cognitive deficits. Whole cell recording and behavior experiments will be involved in my study in the near future. My interests are also in the microglia based link among different physical stress such as hypoxia and inflamation.
Ning Zhou
PhD. in Progress, Neuroscience
BSc. Peking University
My research is focused on the cellular mechanism of spreading depression and ischemic depolarization in cerebral cortex. Spreading depression is thought to be the neural cause of migraine headaches. It is a wave that spreads throughout the gray matter at the front of which brain cells undergo profound depolarization. Understanding the mechanism of spreading depression will also help to reveal the cellular processes of ischemic cell death. My research involves the use of combined techniques, including two-photon laser scanning microscopy and electrophysiology, to discover cellular processes of different types of brain cells during spreading depression, and how this contributes to cell death during stroke.
