Dr. Brian Christie
Effects of exercise on the mechanisms of the brain
Dr. Christie is a neuroscientist studying the effects of exercise on the brain. His laboratory employs a sophisticated array of electrophysiological, immunohistochemical, molecular and behavioral research methods to elucidate learning and memory mechanisms in the aging brain.
He is particularly interested in the hippocampal formation and has conducted studies to examine its role in learning and memory throughout the lifespan. Researchers in the lab also use animal models of disorders such as Alzheimer's disease, fetal alcohol syndrome (FAS) and fragile-X syndrome to understand how neuropathologies can influence hippocampal structure and function.
Dr. Christie has been featured in UVic knowlEDGE
Mailing Address: PO Box 1700 Stn CSC, Victoria, BC V8W2Y2
Research techniques and approach
My research investigates how developmental disorders, and other pathological conditions, affect the structure and function of the hippocampal formation, a part of the brain known to be involved in learning and memory processes. I am particularly interested in how the continual introduction of new neurons into the adult brain can promote enhanced learning and memory.
My work employs several animal models of developmental disorders, including Fetal Alcohol Syndrome, Fragile-X Syndrome and Rett Syndrome. We hypothesize that these disorders affect a common set of structural and functional features in the hippocampus, and that their effects are functionally similar to those observed in Alzheimer's disease and the senescent brain.
In short, all of these disorders involve some degree of altered neurogenesis and synaptic function. I believe that carefully examining what is altered in the hippocampus by each disorder will contribute to a basic understanding of how learning and memory processes occur in the brain.
Many research programs are based around a single technical approach, and while this can have its advantages, in some cases it is somewhat self-limiting in terms of the types of research questions that can be tackled. The research questions of today and tomorrow, more often than not, will require an interdisciplinary approach to make any substantial headway.
In my laboratory, we use a number of sophisticated research techniques in a convergent fashion to assess hippocampal structure and function. For instance, we have recently used behavioural analysis, electrophysiology, and immunohistochemistry to show that prenatal exposure to ethanol can impact hippocampal function well into adulthood.
In addition we have also shown that exercise can largely ameliorate these hippocampal deficits. In these particular experiments we can show that reduced neurogenesis in the hippocampus recovers, that reduced synapse numbers can be restored, that reduced synaptic function can be restored, and most importantly, that behavioral functioning can be restored to normal levels.
In this particular case, we have also just recently become involved in a group of researchers that will try to determine if these same benefits can be seen in humans with FAS/E. This highlights how I like to direct my research to better understand and alleviate a particular problem in an animal model, hopefully in a manner that offers an easy transfer of knowledge to the human population.
Clyde Hertzman, director of the Human Early Learning Partnership (HELP) is fond of using the term "from cell to society", and this really describes the outlook I try to take in my research. I believe that by focusing on how a phenomenon (i.e. neurogenesis) can impact a behavior (i.e. learning) that we will be better able to understand both normal brain function, and how a variety of pathological conditions impact the capacity of the hippocampus.
Ultimately, it is my hope to utilize the knowledge we gain about processes such as neurogenesis to help instigate the brain to actually heal itself, and thereby ameliorate the behavioural deficits that are characteristic of a wide range of disorders that involve neurodegeneration. This may sound grandiose at first, but really we have to look no further than our own skin to see how effective self regenerative mechanisms can be when they respond appropriately.
Antibody directed Immunohistochemistry and other histology techniques
Immunohistochemistry is primarily used in my laboratory to quantify where mitotic activity is occurring, and what phenotypes new cells in the brain are assuming. We can also use immunohistochemical approaches to determine the availability of different proteins at the synapse.
The biggest difference between this technique and the rest of the histological approaches we employ is that the immunohistochemistry requires confocal microscopy to precisely determine the localization of different antibodies in individual cells. We also routinely employ techniques such as Golgi analysis to determine how different manipulations change dendritic profiles, length, and synapse numbers in the hippocampus.
We really employ two distinct forms of electrophysiology in my lab, though both utilize common electrical principles.
The first area involves performing field recordings from specific structures in the brains of anaesthetized animals (in vivo).
In the second area, we use brain slice technology to perform either field or whole-cell recordings from hippocampal neurons in vitro.
Few laboratories in the world have the capacity to address functional questions using both in vitro and in vivo approaches, and I am often sought out to teach in vivo methodologies to other individuals and laboratories from around North America.
Because learning and memory can be quantified in the behaving animal, we often employ different behavioural tasks to determine how well animals learn different hippocampal dependent tasks (i.e. The Morris Water Maze).
Because a variety of factors can influence behavioral performance, we also routinely assay animals for anxiety and motor deficits to determine if these are impairing our capacity to quantify learning abilities in the various animal models we employ.
Most recently we have begun to examine how learning and memory is affected in a patient population in conjunction with the BC Cancer Institute.
We have oligodendroma brain tumor patients referred to us by Dr. Brian Thiessen. We administer a series of brief mnemonic assessment tests to them before, during, and following chemotherapy.
This patient population is high functioning, and uses a chemotherapy agent that does not have severe side effects. Never-the-less, like all chemotherapy agents, it halts mitotic activity in the brain.
Our goal is to determine how this impacts learning and memory in humans -- we are carrying out this work in conjunction with animal experiments to determine exactly how much this drug affects neurogenesis and synaptic transmission in the hippocampus.
Patricia Brocardo – Post Doctoral Fellow
Joana Gil-Mohapel – Research Associate
Mariana Vetrici – Post Doctoral Fellow
|Sonata Yau - Post Doctoral Fellow
Research areas: The functional role of fragile X mental retardation protein on regulating synaptic plasticity in the hippocampus.
Anna Patten - PhD
Mohamed Ghilan - PhD
Research Area: cellular mechanisms and altered receptor contributions to the differential effect of stress on learning and memory in a mouse model of autism and fragile X syndrome. Specific areas of interest are synaptic plasticity, molecular analysis, and behaviour.
Please check out my website at http://www.neuroscienceoflife.com
This website is not affiliated with the University of Victoria and in no way reflects the views of the University of Victoria.
Zoe Sharp - MSc
Research Area: The effect of exercise on neurogenesis in fmr1 KO mice; Neurogenesis(the production and survival of new neurons) is a process which is most active during development but is limited to only a few areas of the adult brain.
Multiple factors can influence neurogenesis including stress, diet, neurological disorders, and exercise. One such disorder is fragile X syndrome (FXS) which is the most common form of inherited intellectual disability and is caused by a mutation of the fmr1 gene on the X chromosome. My research concentrates on a mouse model of FXS and whether voluntary exercise modulates neurogenesis in these animals.
Emily White - MSc
Research Area: Traumatic brain injury (TBI) is the leading cause of death and disability in individuals under 45 years of age. My project will characterize the short and long term deficits brain trauma incurs on hippocampl synaptic plasticity, in an attempt to identify a mechanism of coginitve impairments related to learning and memory observed in yourng individuals who have experienced single or multiple mild TBIs.
2013 New Neuroscience Students
Christine Fontaine, MSc
Alicia Meconi, MSc
Jessica Taylor, Ph.D.
Undergraduate Honors Students
Crystal Bostrom, MSc - Research Technician
Post Doctoral Fellows
|Dr. Helle Sickman, Ph.D. - Helle is currently working as a post-doctoral fellow at the University of Copenhagen and Lundbeck, in Copenhagen Denmark.|
|Dr. Brennan Eadie, Ph.D. - Brennan is currently finishing is MD degree at UBC MED school in Vancouver, BC.|
|Dr. Andrea Titterness, Ph.D. - Andrea is currently a post-doctoral fellow at UBC.|
|Dr. Jennifer Helfer, Ph.D. - Jennifer is currently a post-doctoral fellow in Dr. David Harris' laboratory at Boston University School of Medicine.|
|Dr. Timal Kannangara, Ph.D - Timal is currently a post-doctoral fellow in Dr's. D. Lagace and J.C. Beique in the Faculty of Medicine at University of Ottawa.|
|Namat Majaess, M.Sc. - graduated June 2013|
|Crystal Bostrom, M.Sc. - graduated November 2012|
|Jessica Simpson, M.Sc. - UPDATE - Jessica has been accepted to UBC MED - IMP Victoria commencing September 2012.|
|Fanny Boehme, M.Sc. - Fanny is currently a Ph.D. student in Dr. Kempermann's Lab, Dresden, Germany.|
|James Chin, M.Sc. - James is currently in MED school in Toronto, Ontario.|
|Ross Petersen, M.Sc.|
|Adrian Cox - UPDATE - Adrian has been accepted to UBC MED - IMP Victoria commencing September 2012.|
|Aimee Kernick - UPDATE - Aimee has been accepted to UBC MED - Vancouver commencing September 2012.|
|Kristin Morch - UPDATE - Kristin has been accepted to UBC MED - Kelowna commencing Septemer 2012.|
Research Assistant Volunteer
|Erica Giles - UPDATE - Erica has been accepted to Yale MED school commencing September 2012.|
- Gl-Mohapel J, Simpson JM, Titterness AK, Christie BR. Characterization of the neurogenesis quiescent zone in the rodent brain: effects of age and exercise. Eur J Neurosci. 2010 May; 31(9):1708.
- Gl-Mohapel J, Boehme F, Kainer L, Christie BR. Hippocampal cell loss and neurogenesis after fetal alcohol exposure: Insights from different rodent models. Brain Res Rev. 2010 May 13.
- Hill MN, Titterness AK, Morrish AC, Carrier EJ, Lee TT, Gil-Mohapel J, Gorzalka BB, Hillard CJ, Christie BR . Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus, 2010 Apr; 20(4):513-23.
- Dahlhaus R, Hines RM, Eadie BD, Kannangara TS, Hines DJ, Brown CE, Christie BR, El-Husseini A. Overexpression of the cell adhesion protein neuroligin-1 induces learning deficits and impairs synaptic plasticity by altering the ratio of excitation to inhibition in the hippocampus. Hippocampus. 2010 Feb: 20(2):305-22.
- Connor JM, Franks KM, Titterness AK, Russell K, Merrill DA, Christie BR, Sejnowski TJ, Tuszynski MH. NGF is essential for hippocampal plasticity and learning. Journal of Neuroscience. 2009 29(35) 10883-10889.
- Eadie BD, Zhang WN, Boehme F, Gil-Mohapel J, Kainer L, Simpson JS, Christie BR. Fmr1 knockout mice show reduced anxiety and alterations in neurogenesis that are specific to the ventral dentate gyrus. Neurobiology of Disease, Neurobiol Dis. 2009 Nov;36(2):361-73. Epub 2009 Aug 8.
- Parkinson PF, Kannangara TS, Eadie BD, Burgess BL, Wellington CL, Christie BR. Cognition, learning behavior and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1. Lipids in Health and Disease 2009, 8:5
- Kannangara TS, Webber A, Gil-Mohapel J, Christie BR . Stress differentially regulates the effects of voluntary exercise on cell proliferation in the dentate gyrus of mice. Hippocampus. 2008 Oct 27*=corresponding and senior author.
- Christie BR , Eadie BD, Kannangara TS, Robillard JM, Shin J, Titterness AK. Exercising our brains: how physical activity impacts synaptic plasticity in the dentate gyrus. Neuromolecular Med. 2008; 10(2):47-58l
- Christie BR , Eadie BD, Kannangara TS, Robillard JM, Shin J, Titterness AK. Exercising our brains: how physical activity impacts synaptic plasticity in the dentate gyrus. Neuromolecular Med. 2008; 10(2):47-58l
- Titterness AK, Christie, BR . Long-term depression in vivo: effects of sex, stress, diet, and prenatal ethanol exposure. Hippocampus. 2008; 18(5):481-91
- Fox CJ, Russell K, Titterness AK, Wang YT, Christie BR.* (2007) Tyrosine phosphorylation of the GluR2 subunit is required for long-term depression of synaptic efficacy in young animals in vivo. Hippocampus. 17(8):600-605. *=corresponding and senior author
- Wong TP, Howland JG, Robillard JM, Ge Y, Yu W, Titterness AK, Brebner K, Liu L, Weinberg J, Christie BR, Phillips AG, Wang YT. (2007) Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment. PNAS. 104(27):11471-11476.
- Vasuta C, Caunt C, James R, Samadi S, Schibuk E, Kannangara T, Titterness AK, Christie BR.* (2007) Effects of exercise on NMDA receptor subunit contributions to bidirectional synaptic plasticity in the mouse dentate gyrus. Hippocampus. 17(12):1201-1208. *=corresponding and senior author.
- Ernst, C., Olson, A.K., Pinel, J.P., Lam, R., and Christie, B.R.* (2006) Antidepressant effects of exercise: Evidence for an adult-neurogenesis hypothesis? Journal of Psychiatry and Neuroscience. 31(2):84-93. *=corresponding and senior author
- Fox, C.J., Russell, K., Wang, Y.T., and Christie, B.R.* (2006) Contribution of NR2A and NR2B NMDA subunits to bidirectional synaptic plasticity in the hippocampus in vivo. Hippocampus. 16(11):907-15. *=corresponding and senior author
- Ernst, C., Christie, B.R.* (2005) The putative neural stem cell marker, Nestin, is expressed in heterogenous cell types in the adult rat neocortex. Neuroscience. 138(1):183-8. Epub 2005 Dec 15. *=corresponding and senior author
- Christie, B.R., and Cameron, H.A. (2006) Neurogenesis in the adult hippocampus. Hippocampus. 16(3):199-207. *=corresponding and senior author
- Olson, A.K., Eadie, B.D., Ernst, C., and Christie, B.R.* (2006) Environmental enrichment and voluntary exercise increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus. 16(3):250-60. *=corresponding and senior author
- Ernst, C. , Christie, B.R.* (2005) Nestin-expressing cells and their relationship to mitotically active cells in the subventricular zones of the adult rat. European Journal of Neuroscience. 22(12):3059-66. *=corresponding and senior author
- Redila. V., Olson, A., Swann, S.E., Mohades, G., Webber, A., Weinberg, J., Christie, B.R.*(2006) Hippocampal neurogenesis is reduced following prenatal ethanol exposure but can be rescued with voluntary exercise. Hippocampus. 16(3):305-11. Work was performed in my lab at UBC. I included Dr. Weinberg as an author to acknowledge her contribution in helping us establish her prenatal ethanol paradigm in my laboratory. *=corresponding and senior author
- Ernst, C., Christie, B.R.* (2006) Temporally Specific Proliferation Events Are Induced In The Hippocampus Following Acute Focal Injury. Journal of Neuroscience Research. 83(3):349-61 Work was performed in my lab at UBC. *=corresponding and senior author
- Redila, V., Christie, B.R.* (2006) Exercise Induced Changes in Dendritic Structure and Complexity in the Adult Hippocampal Dentate Gyrus. Neuroscience. 137(4):1299-307. Epub 2005 Dec 9. Work was performed in my lab at UBC.I *=corresponding and senior author
- Ernst, C., Christie, B.R.* (2005) Isolectin GS-IB4 as a vascular stain for the study of adult neurogenesis. Journal of Neuroscience Methods. 137(3):1031-7. Epub 2005 Nov 14. Work was performed in my lab at UBC. *=corresponding and senior author
- Christie, B.R., Li, A., Wong, B.K.Y., Lieblich, S., Booth, H., Eadie, B., Redila,V., Ernst, C., Simpson, E. (2006) Deletion of the nuclear receptor Nr2e1 impairs synaptic plasticity and dendritic structure in the mouse dentate gyrus. Neuroscience. (Epub available ahead of print ) This work was performed in my laboratory using knock-out mice generated by Dr. Elizabeth Simpson and Bibiana Wong.
- Froc, D., Christie, B.R.*(2005) Corticotropin-releasing hormone induces long-term depression of synaptic transmission in rat sensorimotor cortex in vivo. Neuroscience. 134(3):965-973 . All work was performed in my lab at UBC. *=corresponding and senior author
- Christie, B.R.* , Swann, S.E., Fox, C.J., Froc, D., Lieblich, S.E., Redila, V., Webber, A. (2005) Voluntary exercise rescues deficits in spatial memory and long-term potentiation in prenatal ethanol-exposed male rats. European Journal of Neuroscience. (22)1: 1719-1726. All work was performed in my lab at UBC. *=corresponding and senior author
- Eadie, B., Redila, V., Christie, B.R.* (2005) Voluntary exercise alters the cyto-architecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density. Journal of Comparative Neurology. 486(1): 39-47. Work was performed in my lab at UBC. Paper was used for a Master’s thesis for B. Eadie. *=corresponding and senior author
- Hill, M., Froc, D., Fox, C., Gorzalka, B., Christie, B.R.*(2004) Prolonged cannabinoid treatment results in spatial working memory deficits and impaired long-term potentiation in the CA1 region of the hippocampus in vivo. European Journal of Neuroscience. (20)3: 859-863. Supervised behavioral and electrophysiological work done in my UBC lab on paper in collaboration with Dr. Gorzalka’s student. *=corresponding and senior author
- Farmer , J., Zhao, X., van Praag, H., Wodtke, K., Gage, F.H., Christie, B.R.* (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience. 124(1): 71-79. This was thesis work was performed by my students Joel Farmer and Karl Wodtke. PCR analysis was done by members of Dr. Gage’s lab. *=corresponding and senior author
- Johnston, D., Christie, B.R., Frick, A., Gray, R., Hoffman, D.A., Schexnayder, L.K., Watanabe, S., and Yuan, L-L. (2003) Active dendrites, potassium channels, and synaptic plasticity. Philos Trans R Soc Lond B Biol Sci. 358(1432): 667-74. I contributed the second most to this review paper. Order of authorship was based upon the degree of contribution.
- Froc, D., Li, A., Eadie, B., Wodtke, K., Tse, M., Christie, B.R.* (2003) Reduced Synaptic Plasticity in the Lateral Perforant Path Input to the Dentate Gyrus of Aged C57BL/6 Mice. Journal of Neurophysiology. 90(1): 32-8. This work is the first publication performed completely in my laboratory at UBC, solely by members of my laboratory. *=corresponding and senior author
- Zhao, X., Ueba, T., Christie, B.R., Barkho, B., McConnell, MJ., Nakashima, K., Lein, E.S., Eadie, B., Willhoite, A.R., Muotri, A.R., Summers, R.G., Chun, J., Lee, K-F., Gage, F.H. (2003) Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function. Proceedings National Academy of Science U. S. A. 100(11): 6777-6782. My student Brennan Eadie and I performed electrophysiological experiments for this paper.
- van Praag H.*, Schinder, A.*, Christie, B.R.*, Palmer, T.D., Gage, F.H. (2002) Functional Neurogenesis in the Adult Hippocampus. Nature. 415: 1030-1034. *Astericks indicate that these individuals shared first authorship equally, as indicated in footnote of this article. I performed the electrophysiological studies in this paper while at UBC.
- Vissel, B., Royle, G.A., Christie, B.R., Schiffer, H.H., Ghetti, A., Tritto, T., Perez-Otano, I., Radcliffe, R.A., Seamans, J., Sejnowski, T., Wehner, J.M., Collins, A.C., O’Gorman, S., Heinemann, S.F. (2001) The role of RNA editing of kainate receptors in synaptic plasticity and seizures . Neuron. 29: 217-227.
- Seamans J.K., Durstewitz D., Christie, B.R., Stevens C.F., Sejnowski T.J. (2001) Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons . Proceedings National Academy of Science U. S. A. 98(1): 301-306.
- Christie, B.R., Franks, K., Seamans, J. K., Saga, K., Sejnowski, T.J. (2000) Synaptic Plasticity in Morphologically Identified CA1 Stratum Radiatum Interneurons and Projection Cells . Hippocampus. 10: 673-683.
- Van Praag, H. *, Christie, B.R.*, Sejnowski, T.J., Gage, F.H. (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice . Proceedings National Academy of Science U. S. A. 96(23): 13427-13431. *Astericks indicate that these individuals shared first authorship equally, as indicated in footnote of this article.
- Christie, B.R. , Schexnayder, L.K., Johnston, D. (1997) Contribution of voltage-gated calcium channels to homosynaptic long-term depression (LTD) in the CA1 region in vitro . Journal of Neurophysiology.77: 1651-1655.
- Christie, B.R., Magee, J.C., Johnston, D. (1996) Dendritic calcium channels and hippocampal long-term depression . Hippocampus. 6(1): 17-23.
- Christie, B.R. (1996) Hippocampal long-term depression . Hippocampus. 6(1): 1-2. corresponding and senior author
- Johnston, D., Magee, J. C., Colbert, C. M., Christie, B.R.(1996) Active properties of neuronal dendrites. Annual Reviews of Neuroscience. 19: 165-186.
- Christie, B.R., Magee, J.C., Johnston, D. (1996) The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons. Learning and Memory. 3: 160-169.
- Magee, J.C., Avery, R.B., Christie, B.R., Johnston, D. (1996) Dihydropyridine-sensitive voltage-gated calcium channels contribute to the resting intracellular calcium concentration of hippocampal CA1 pyramidal neurons. Journal of Neurophysiology. 76(5): 3460-3470.
- Magee, J.C., Christofi, G., Miyakawa, H., Christie, B.R., Lasser-Ross, N., Johnston, D. (1995) Subthreshold synaptic activation of voltage-gated Ca2+ channels mediates a localized Ca2+ influx into the dendrites of hippocampal pyramidal neurons. Journal of Neurophysiology. 74(3): 1335-1342.
- Christie, B.R. , Stellwagon, D., Abraham, W.C. (1995) Evidence for common expression mechanisms underlying heterosynaptic and associative long-term depression in the dentate gyrus. Journal of Neurophysiology. 74(3): 1244-1247.
- Christie, B.R. , Eliot, L.S., Ito, K., Miyakawa, H., Johnston, D. (1995) Different Ca2+ channels in soma and dendrites of hippocampal pyramidal neurons mediate spike-induced Ca2+ influx. Journal of Neurophysiology. 73(6): 2553-2558
- Christie, B.R. , Stellwagon, D., Abraham, W.C. (1995) Reduction in the threshold for long-term potentiation by prior theta-frequency synaptic activity . Hippocampus. 5(1): 52-59.
- Christie, B.R. , Kerr, D.S., Abraham, W.C. (1994) The flip side of synaptic plasticity: An examination of hippocampal LTD mechanisms. Hippocampus. 4(2): 127-135.
- Abraham, W.C., Christie, B.R., Logan, B., Lawlor, P., Dragunow, M. (1994) Immediate early gene expression associated with the persistence of long-term depression in the hippocampus. Proceedings of the National Academy of Sciences USA. 91(21): 10049-10053.
- Christie, B.R. , Abraham, W.C. (1994) L-type voltage-sensitive calcium channel antagonists block heterosynaptic long-term depression in the dentate gyrus of anaesthetized rats . Neuroscience Letters. 167: 41-45.
- Christie, B.R. , Abraham, W.C. (1994) Differential regulation of paired-pulse plasticity following LTP in the dentate gyrus. Neuroreport. 5: 385-388.
- Christie, B.R. , Abraham, W.C. (1992) Priming of associative long-term depression by theta-frequency synaptic activity. Neuron. 9: 79-84.
- Christie, B.R. , Abraham, W.C. (1992) Long-term depression is non-associative and NMDA-dependent in the dentate gyrus of anaesthetized rats. Synapse. 10: 1-6.
- Smythe, J.W., Christie, B.R., Colom, L.V., Lawson, V.H., Bland, B.H. (1991) Hippocampal theta field activity and theta-on/theta-off cell discharges are controlled by an ascending hypothalamo-septal pathway. Journal of Neuroscience. 11(7): 2241-2248.
- Colom, L.V., Christie, B.R., Bland, B.H. (1988) Cingulate cell discharge patterns related to hippocampal EEG and their modulation by nicotinic and muscarinic agents. Brain Research. 460: 329-338.
There are no positions available at this time.