Chao Tai, PhD :

Chao Tai, PhD

During my PhD studies, I have been using multiple methods including electrophysiological, pharmacological, biochemical and two-photon imaging techniques to study the muscarinic modulations of several Ca2+-permeable ion channels in the CNS, and the impacts of these modulations in several brain disorders and activities. The brain’s cholinergic system plays a key role in modulating neuronal excitability, synaptic plasticity and neuronal intrinsic properties. It is also implicated in many brain disorders including Alzheimer’s disease, epilepsy and stroke. The diverse impact of the cholinergic system arises from the extensive number of ion channels that are modulated by acetylcholine. I have also been studing cholinergic modulation of several ion channels and the potential functions of these modulations:  1) Muscarinic enhancement of R-type calcium currents contributes to theta oscillations; 2) Muscarinic-induced translocation of TRPC5 channels contributes to plateau potential in seizures; 3) Muscarinic modulation of NMDA receptors contributes to synaptic plasticity.

taichao@interchange.ubc.ca
Chao Tai, PhD :
Chao Tai, PhD

Chao Tai, PhD

During my PhD studies, I have been using multiple methods including electrophysiological, pharmacological, biochemical and two-photon imaging techniques to study the muscarinic modulations of several Ca2+-permeable ion channels in the CNS, and the impacts of these modulations in several brain disorders and activities. The brain’s cholinergic system plays a key role in modulating neuronal excitability, synaptic plasticity and neuronal intrinsic properties. It is also implicated in many brain disorders including Alzheimer’s disease, epilepsy and stroke. The diverse impact of the cholinergic system arises from the extensive number of ion channels that are modulated by acetylcholine. I have also been studing cholinergic modulation of several ion channels and the potential functions of these modulations:  1) Muscarinic enhancement of R-type calcium currents contributes to theta oscillations; 2) Muscarinic-induced translocation of TRPC5 channels contributes to plateau potential in seizures; 3) Muscarinic modulation of NMDA receptors contributes to synaptic plasticity.

taichao@interchange.ubc.ca
Chao Tai, PhD
Masanori Tachikawa, PhD :

Masanori Tachikawa, PhD

My current research has been mainly focused on the physiological function and regulation of the blood-brain barrier (BBB). The BBB forms complex tight junctions of brain microvascular endothelial cells. I and my colleagues have discovered that various influx and efflux transporters at the BBB function as supporting and protecting systems for the brain. Although these BBB functions must be closely related with the cerebral blood flow and various neural conditions (i.e., inflammation) the mechanism of the relationship between the BBB, glia and neuron remains to be fully understood. It has been proposed that astrocytes, a type of glial cell in the brain, are key players in coordinating in the neuro-vascular coupling. I am now interested in the field of research on calcium signaling in astrocyte and its role in cerebral blood flow and inflammation, using two-photon laser scanning microscopy in acute brain slices of the hippocampus and cortex.

tachi@mopera.net
Masanori Tachikawa, PhD :
Masanori Tachikawa, PhD

Masanori Tachikawa, PhD

My current research has been mainly focused on the physiological function and regulation of the blood-brain barrier (BBB). The BBB forms complex tight junctions of brain microvascular endothelial cells. I and my colleagues have discovered that various influx and efflux transporters at the BBB function as supporting and protecting systems for the brain. Although these BBB functions must be closely related with the cerebral blood flow and various neural conditions (i.e., inflammation) the mechanism of the relationship between the BBB, glia and neuron remains to be fully understood. It has been proposed that astrocytes, a type of glial cell in the brain, are key players in coordinating in the neuro-vascular coupling. I am now interested in the field of research on calcium signaling in astrocyte and its role in cerebral blood flow and inflammation, using two-photon laser scanning microscopy in acute brain slices of the hippocampus and cortex.

tachi@mopera.net
Masanori Tachikawa, PhD
Dustin Hines, PhD :

Dustin Hines, PhD

Dustin Hines completed his PhD. in May 2009. His thesis title was : "The Roles of Microglia in Response to Pathological Stimuli in the Brain". Dustin moved shortly thereafter to Boston, where he is now working as a post-doc at the University of Boston for Dr. P. Hayden, and is continuing his research in the roles for astrocyte regulation of behavior.

dhines@interchange.ubc.ca
Dustin Hines, PhD :
Dustin Hines, PhD

Dustin Hines, PhD

Dustin Hines completed his PhD. in May 2009. His thesis title was : "The Roles of Microglia in Response to Pathological Stimuli in the Brain". Dustin moved shortly thereafter to Boston, where he is now working as a post-doc at the University of Boston for Dr. P. Hayden, and is continuing his research in the roles for astrocyte regulation of behavior.

dhines@interchange.ubc.ca
Dustin Hines, PhD
Julie Robillard, PhD :

Julie Robillard, PhD

The aging process translates into many changes in the brain. The functional properties of hippocampal activity are particularly susceptible to aging, and aged animals display significant calcium (Ca2+) dysregulation in the hippocampal pyramidal cells. This dysregulation in turn impairs synaptic plasticity that involves Ca2+-dependent processes, and it has been established that hippocampal long-term potentiation (LTP), a cellular model for learning and memory, is altered in aged animals. The goal of my research is to use naturally aging mice and a combination of electrophysiology and molecular biology techniques to determine more precisely how aging affects different forms of synaptic plasticity in the mouse hippocampus, and to investigate what mechanisms are responsible for these changes.

jrobilla@gmail.com
Julie Robillard, PhD :
Julie Robillard, PhD

Julie Robillard, PhD

The aging process translates into many changes in the brain. The functional properties of hippocampal activity are particularly susceptible to aging, and aged animals display significant calcium (Ca2+) dysregulation in the hippocampal pyramidal cells. This dysregulation in turn impairs synaptic plasticity that involves Ca2+-dependent processes, and it has been established that hippocampal long-term potentiation (LTP), a cellular model for learning and memory, is altered in aged animals. The goal of my research is to use naturally aging mice and a combination of electrophysiology and molecular biology techniques to determine more precisely how aging affects different forms of synaptic plasticity in the mouse hippocampus, and to investigate what mechanisms are responsible for these changes.

jrobilla@gmail.com
Julie Robillard, PhD
Grant Gordon, PhD :

Grant Gordon, PhD

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.

grjgordo@gmail.com
Grant Gordon, PhD :
Grant Gordon, PhD

Grant Gordon, PhD

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.

grjgordo@gmail.com
Grant Gordon, PhD
Denise Feighan, BSc :

Denise Feighan, BSc

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.

Denise Feighan, BSc :
Denise Feighan, BSc

Denise Feighan, BSc

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.

Denise Feighan, BSc
Ning Zhou, PhD :

Ning Zhou, PhD

Dr. Zhou completed her PhD. in 2010 with Brian MacVicar and now has a Post-Doctoral Fellowship in the lab. She is funded by the Taiwan Department of Health Clinical Trial and Research Centre of Excellence, where she has accepted a Professorship beginning in late 2011.

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.

ning.zhou@interchange.ubc.ca
Ning Zhou, PhD :
Ning Zhou, PhD

Ning Zhou, PhD

Dr. Zhou completed her PhD. in 2010 with Brian MacVicar and now has a Post-Doctoral Fellowship in the lab. She is funded by the Taiwan Department of Health Clinical Trial and Research Centre of Excellence, where she has accepted a Professorship beginning in late 2011.

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.

ning.zhou@interchange.ubc.ca
Ning Zhou, PhD
Zachary Stansfield, MSc :

Zachary Stansfield, MSc

In 2010, I completed my BSc in Psychology with a minor in Neuroscience from the University of Guelph. During 2008 I held an NSERC USRA in Vision Science in the laboratory of Dr. Allison Sekuler at McMaster University where I conducted research on the physiological and psychological correlates of image processing. Throughout the rest of my undergraduate studies I conducted research in a number of laboratories on both the cognitive and cellular bases of memory and memory dysfunction.

My research interests lie at the intersection between physiology and behaviour. In particular, I am intrigued by the cellular correlates of memory and how these cellular events are expressed behaviourally. In addition, I am also interested in exploring the underlying physiological abnormalities associated with pathologies such as stroke, MS and neurodegeneration.

Past research has shown that neuroglial metabolic coupling is intrinsic to brain function in vivo, particularly for glutamate and energy metabolism. My current research focuses on mechanisms of metabolic coupling between astrocytes and neurons during normal synaptic activity and conditions of abnormal cellular stress. More specifically, my research aims to explore the role of energy metabolism in basic processes associated with ischemic stroke and models of plasticity such as long term potentiation.

zstansfi@gmail.com
Zachary Stansfield, MSc :
Zachary Stansfield, MSc

Zachary Stansfield, MSc

In 2010, I completed my BSc in Psychology with a minor in Neuroscience from the University of Guelph. During 2008 I held an NSERC USRA in Vision Science in the laboratory of Dr. Allison Sekuler at McMaster University where I conducted research on the physiological and psychological correlates of image processing. Throughout the rest of my undergraduate studies I conducted research in a number of laboratories on both the cognitive and cellular bases of memory and memory dysfunction.

My research interests lie at the intersection between physiology and behaviour. In particular, I am intrigued by the cellular correlates of memory and how these cellular events are expressed behaviourally. In addition, I am also interested in exploring the underlying physiological abnormalities associated with pathologies such as stroke, MS and neurodegeneration.

Past research has shown that neuroglial metabolic coupling is intrinsic to brain function in vivo, particularly for glutamate and energy metabolism. My current research focuses on mechanisms of metabolic coupling between astrocytes and neurons during normal synaptic activity and conditions of abnormal cellular stress. More specifically, my research aims to explore the role of energy metabolism in basic processes associated with ischemic stroke and models of plasticity such as long term potentiation.

zstansfi@gmail.com
Zachary Stansfield, MSc
Clare Howarth, PhD : Leducq Postdoctoral Fellow

Clare Howarth, PhD

Leducq Postdoctoral Fellow

Dr. Howarth is one of Brian MacVicar's Leducq Fellows. She is the recipient of the 2011 Canadian Post-Doctoral Research Fellowship, and is a Sir Henry Wellcome Postdoctoral Fellow.

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.

chowarth@interchange.ubc.ca
Clare Howarth, PhD : Leducq Postdoctoral Fellow
Clare Howarth, PhD

Clare Howarth, PhD

Leducq Postdoctoral Fellow

Dr. Howarth is one of Brian MacVicar's Leducq Fellows. She is the recipient of the 2011 Canadian Post-Doctoral Research Fellowship, and is a Sir Henry Wellcome Postdoctoral Fellow.

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.

chowarth@interchange.ubc.ca
Clare Howarth, PhD