Brian MacVicar, PhD

Brian MacVicar, PhD.

Brain Research Centre

Department of Psychiatry

After completing his PhD in Neurophysiology from the University of Toronto in 1980, Brian MacVicar went on to postdoctoral training in Neuroscience first at Michigan State University, then at New York University Medical School. Within the first few years of then being appointed to Associate Professor at the University of Calgary, he developed a research program designed to analyze the properties of astrocytes with a view showing that astrocytes  are not passive cells, and soon discovered that these cells have high voltage-gated calcium channels.  This discovery  started the field of studying active membrane properties of glial cells. With his colleagues  (Basarsky et al., 1998), they  analyzed the calcium signaling properties of astrocytes in intact brain tissue to determine how astrocyte calcium responses might influence neurons, while simultaneously mapping spreading depression and intracellular calcium to determine the relationship between calcium waves in astrocytes and spreading depression.

In 1990, the MacVicar lab developed imaging techniques to monitor intrinsic optical signals in brain tissue, and were the first researchers ever to image synaptic activation in brain slices and in the isolated whole brain preparation (MacVicar et al., 1991; Federico et al, 1994) and during human operations (MacVicar et al., US Patent# 5,215,095). He developed software for imaging experiments, licensed to Axon Instruments (Axon Imaging Workbench) for world-wide distribution and is now sold to INDEC. Dr. MacVicar was also the first to describe using infrared video imaging to observe cells in brain slices.  This technique is now widely used to visualize neurons in brain slices for patch recordings (MacVicar,   1984).

Dr. MacVicar started his research in plateau potentials in the mid 1990’s, soon discovering that plateau potentials can be evoked in hippocampus pyramidal neurons from muscarinic enhancement of calcium activated non-specific (CAN) cation channels (Fraser & MacVicar, 1996) which he  and his colleagues identified as cGMP gated channels (Kuzmiski & MacVicar, 2001). It was also discovered that cholinergic stimulation evokes plateau potentials by selectively enhancing R-type calcium currents in addition (Tai et al, 2006) and that the enhanced R-type calcium spikes are targets for the anticonvulsant, topiramate. 

In 2003, he moved his lab to the Brain Research Centre, and became a Professor in the Department of Psychiatry at the University of British Columbia, where he has been continuing with his research since.

Two-photon laser scanning microscopy is yet another area of expertise for Dr. MacVicar. He, along with his colleagues, have used this technique in the uncaging of calcium, and have found unequivocally that calcium transients in identified astrocytes cause vascular constrictions thereby regulating cerebral blood flow (Mulligan & MacVicar,  2004).  This was the first clear functional role for astrocyte calcium signaling in astrocytes.

Dr. MacVicar and his colleagues (Thompson et al., 2006)  made the important discovery that ischemia triggers the opening of gap junction hemichannels in neurons. A follow-up  paper in Science (Thompson et al., 2008) describes how the pannexin hemichannel can contribute to seizure discharges when it is activated by NMDA receptor stimulation.  As a graduate student,  Dr. MacVicar had  discovered for the first time that neurons in the hippocampus are electrotonically coupled.  This was the first direct demonstration of electrotonic coupling in the mammalian CNS.  The evidence was obtained using simultaneous dual intracellular recordings from neurons in hippocampal brain slices (MacVicar &  Dudek, 1981).

Most recently, Dr. MacVicar and his colleagues used two-photon laser scanning microscopy and uncaging of calcium to show unequivocally that calcium transients in identified astrocytes cause vascular constrictions thereby regulating cerebral blood flow (Mulligan & MacVicar 2004 Nature 431:195). In Gordon et al, 2008 Nature, they continued this work by showing that astrocytes regulate both dilation and constriction of adjacent arterioles via a complex response to metabolic changes. This provides new insight into how the brain intrinsically regulates its own blood supply and into the pathological changes in cbf observed following stroke, SAH and vascular dementias.

Recently awarded directorship of the prestigious Leducq Foundation Transatlantic Networks of Excellence Program, Dr. MacVicar is currently leading this multi-site, international collaborative five year research program.  He is responsible for overseeing the progress of this large scale program, and reporting key findings. He also has been awarded many research grants over the past two decades, such as the Canadian Institutes for Health Research, the Michael Smith Foundation for Health Research, the Medical Research Council, the Alberta Heritage Foundation for Medical Research, the National Centres of Excellence, the Heart and Stroke Foundation, and many more.  

Dr. MacVicar is currently continuing his research, while supervising and running a lab of 12 funded PhD and post-doctoral fellows.  Here he mentors his students on experimental techniques and cutting edge research.