Dr. Craig Brown
Cellular and molecular mechanisms of neuronal plasticity
Top Left: In vivo voltage sensitive dye imaging of whisker-evoked depolarizations in the barrel cortex. Note that depolarizations (warm colors) are prominent in the barrel-field and secondary somatosensory cortex (right side of barrel-field). Top right: Low magnification confocal image showing the distribution of GABA-ergic neurons (red) in the barrel-field. Bottom right: High magnification confocal image reveals that YFP labelled alpha-4 nAChRs target GABA-ergic neurons in layer 4. Bottom left: Electron micrograph showing that alpha-4 nAChRs are expressed in neuronal cell bodies in putative peri/extra synaptic regions.
Brown CE, Sweetnam D, Beange M, Nahirney PC, Nashmi R. 2012. Alpha-4 nicotinic acetylcholine receptors modulate experience-based cortical depression in the adult somatosensory cortex. Journal of Neuroscience: 32(4): 1207-1219.
Researching experience-dependent neuronal plasticity in the cerebral cortex.
Shown above: Synaptic zinc staining levels in the mouse barrel cortex are rapidly regulated by whisker experience. Darker barrels correspond to facial whiskers plucked in a checkerboard pattern. Data collected in collaboration with Dr. Richard Dyck (U Calgary).
Brown CE and Dyck RH. 2005. Modulation of synaptic zinc in barrel cortex by whisker stimulation. Neuroscience 134:355-359.
Diabetes and stroke research
Understanding impact of diabetes and stroke on neuronal and vascular function.
"In vivo voltage sensitive dye imaging reveals impaired cortical re-mapping of the forelimb sensory representation 14 weeks after stroke in diabetic and insulin treated mice. A: Montage shows forelimb evoked cortical depolarizations in sham stroke non-diabetic and diabetic mice. B: Montage shows the loss of forelimb-evoked cortical responses in regions next to stroke (indicated by white circle) in both non-diabetic and diabetic mice. After 14 weeks recovery from stroke, cortical responses to the forepaw re-emerge in peri-infarct cortex of non-diabetic. However, this re-mapping is significantly impaired in diabetic mice, as well as diabetic mice that had blood sugar levels controlled after stroke with insulin."
For more details see: Sweetnam D, Holmes A, Tennant K, Zamani A, Walle M, Jones P, Wong C, Brown CE. 2012 Diabetes impairs cortical plasticity and functional recovery following ischemic stroke. Journal of Neuroscience 32(15):5132-5143.
Investigation of higher-order information processing centers
Investigation of higher-order information processing centers
Shown above: Functional characterization of secondary somatosensory cortex using optical/dye based imaging techniques and neuronal tracers.
(S1FL, Primary Somatosensory Forelimb Cortex. S2, Secondary Somatosensory Cortex)
- Tennant K and Brown CE. Diabetes augments in vivo microvascular blood flow dynamics after stroke. Journal of Neuroscience.
- Sweetnam D and Brown CE. 2013. Stroke induces long-lasting deficits in the temporal fidelity of sensory processing in the somatosensory cortex. Journal of Cerebral Blood Flow and Metabolism 33(1):91-96.
- Sweetnam D, Holme A, Tennant KA, Zamani A, Walle M, Jone P, Wong C, Brown CE*2012. Diabetes impairs cortical plasticity and functional recovery following ischemic stroke. Journal of Neuroscience:32(15):5132-5143 Full text PDF
- Brown CE, Sweetnam D, Beange M, Nahirnery PC, Nashmi R. 2012. Alpha 4 nicotinic acetylcholine receptors modulate experience-based cortical depression in the adult somatosensory cortex. Journal of Neuroscience :32(4):1207-1219 Full Text PDF
- Brown CE, Boyd JD and Murphy TH. 2010. Longitudinal in vivo imaging reveals balanced and branch specific dendritic remodeling of mature cortical pyramidal neurons after stroke. Journal of Cerebral Blood Flow and Metabolism . 30(4):783-91 .
- Brown CE, Aminoltejari K, Erb H, Winship IR and Murphy TH. 2009. In vivo voltage sensitive dye imaging in adult mice reveals that somatosensory maps lost to stroke are replaced over weeks by new structural and functional circuits with prolonged modes of activation within both the peri-infarct zone and distant sites. Journal of Neuroscience 29:1719-1734.
- Dahlhaus R, Hines RM, Eadie B, Kannangara T, Hines DJ, Brown CE, Christie BR, El-Husseini A. 2009-in press. Over expression 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 . 20(2):305-22.
- Brown CE and Murphy TH. 2008. Livin' on the edge: Imaging dendritic spine turnover in the peri-infarct zone during ischemic stroke and recovery. The Neuroscientist 14:139-146.
- Brown CE, Wong C and Murphy TH. 2008. Rapid morphological plasticity of peri-infarct dendritic spines after focal ischemic stroke. Stroke 39:1286-1291.
- Liu RR, Brown CE, Murphy TH. 2007. Differential regulation of cell proliferation in neurogenic zones in mice lacking cystine transport by xCT. Biochemical Biophysical Research Communications 364:528-533.
- Brown CE, Li P, Boyd JD, Delaney KR and Murphy TH. 2007. Extensive turnover of dendritic spines and vascular remodelling in cortical tissues recovering from stroke. Journal of Neuroscience 27:4101-4109.
- Flynn C, Brown CE, Galasso SL, McIntyre DC, Teskey GC, Dyck RH. 2007. Zincergic innervation of the forebrain distinguishes epilepsy- prone from epilepsy-resistant rat strains. Neuroscience 144:1409-1414.
- Brown CE and Dyck RH. 2005. Modulation of synaptic zinc in barrel cortex by whisker stimulation. Neuroscience 134:355-359.
- Brown CE and Dyck RH. 2005. Retrograde tracing of the subset of afferent connections in mouse barrel cortex provided by zincergic neurons. Journal of Comparative Neurology 486:48-60.
- Brown CE and Dyck RH. 2004. Distribution of zincergic neurons in the mouse forebrain. Journal of Comparative Neurology 479:156-167.
- Schuurmans C, Armant O, Nieto M, Stenman JM, Britz O, Klenin N, Seibt J, Brown C, Tang H, Cunningham JM, Dyck R, Walsh C, Campbell K, Polleux F, Guillemot F. 2004. Sequential phases of neocortical fate specification involve Neurogenin-dependent and independent pathways. EMBO Journal 23:2892-2902.
- Brown CE and Dyck RH. 2003. An improved method for visualizing the cell bodies of zincergic neurons. Journal of Neuroscience Methods 129:41-47.
- Brown CE and Dyck RH. 2003. Experience-dependent regulation of synaptic zinc is impaired in the cortex of aged mice. Neuroscience 119:795-801.
- Brown CE, Seif I, De Maeyer E, Dyck RH. 2003. Altered zincergic innervation of the developing primary somatosensory cortex in monoamine-oxidase A knockout mice. Developmental Brain Research 142:19-29.
- Brown CE and Dyck RH. 2002. Rapid, experience-dependent changes in levels of synaptic zinc in primary somatosensory cortex of the adult mouse. Journal of Neuroscience 22:2617-2625.
Understanding the structural and functional plasticity of cerebral cortical circuits
Dr. Brown's neurobiology lab employs in vivo microscopic imaging technologies such as two-photon microscopy and functional imaging of neuronal and hemodynamic activity that allow the visualization of neuronal structures deep within the living brain or the processing of sensory information in real-time.
A central goal of Dr. Brown's research program is to use these experimental approaches to characterize the neurobiological mechanisms that allow the cerebral cortex to develop normally and change throughout life in response to new experiences (eg. learning, drug exposure) or pathology such as stroke or diabetes.
Mailing Address: PO Box 1700 Stn CSC, Victoria, BC V8W2Y2
Abdul Shehata, Ph.D., Neuroscience Graduate Program
Area of Interest: My research focuses on learning and memory under the umbrella of cortical plasticity. We have developed an associative learning paradigm in which mice must learn to distinguish between two stimuli presented simultaneously and each stimulus presented individually. Once the task is learned we will measure changes in cortical responsiveness using VSD imaging and attempt to manipulate the expression of the associative memory using optogenetics.
Patrick Reeson, Ph.D., Neuroscience Graduate Program
Area of Interest: Diabetics are more likely to suffer a stroke, and when they do their prognosis for recovery is significantly worse. Previous work in the lab has established that the surviving cortical tissue in the diabetic brain is impaired in its ability to adapt to facilitate recovery. Given the importance of the cerebraovasculature to neuronal function and the widespread vascular pathologies associeated with diabetes, Patrick's work aims to understand how vascular dysfunction in the diabetic brain after stroke impairs plasticity and recovery. Patrick utilizes confocal and 2 photon microscopy to image the cerebrovasculature as well as molecular methods to study key angiogenic and vascular permeability factors such as VEGF.
Kelly Tennant, Ph.D. Post Doctoral Fellow
Research Interests: how diabetes negatively affects recovery of function following stroke. Kelly uses in-vivo two-photon imaging combined with behavioural measures of forelimb function to determine how changes in neurons and vasculature contribute to poor post-stroke recovery in diabetic mice. She is a recipient of a Michael Smith Foundation for Health Research postdoctoral fellowship.
Kim Gerrow, Ph.D. Post Doctoral Fellow
Research Interests: Nicotinic receptors in the brain have a very wisespread distribution and their activity controls important aspects of neuronal communication and are involved in nictotine dependence, mood disorders, neurodegeneration and neuroprotection. Despite their importance, many aspects of nicotinic receptor trafficking are unknown. I am interested in understanding the mechanisms that control nicotinic receptor trafficking in the cerebral cortex in vivo.
|Stephanie Friesen, BSc, Research Assistant|
Dustin Trudeau, BSc, Research Assistant
This could be you! We are currently seeking applications for new lab members. Please contact Dr. Brown for details at firstname.lastname@example.org.
Heart and Stroke Foundation of BC & Yukon
Peripheral nerve stimulation to enhance recovery from ischemic cerebral stroke.
Canadian Institute of Health Research (CIHR)
"CIHR New Investigator Award"
Imaging the impact of diabetes on brain function and recovery from stroke.
NSERC Discovery Grant
Imaging rapid, use-dependent plasticity in adult somatosensory cortex.
NSERC Equipment Grant
Equipment for imaging functional domains in the cerebral cortex.
Canada Foundation for Innovation (CFI)
Two-photon microscope for imaging neuronal and vascular circuit assembly and remodeling in the living brain
Michael Smith Foundation for Health Research - Career Investigator Award
Research focus on understanding the mechanisms of experience and injury based cortical plasticity.
Angela Seto - MSc Student
June 10, 2013, Angela successfully defended her MSc thesis titled: Role of the a4B2 nicotinic acetylcholine receptor in stroke recovery.
Andrew Sweetnam-Holmes - MSc Student
August 15, 2013, Andrew successfully defended his MSc thesis titled: Diabetes exacerbates the loss of dendritic spines after ischemic stroke
Dani Sweetnam-Holmes - MSc Student
November 2011, Dani successfully defended her MSc thesis titled "Diabetes impairs cortical plasticity and functional recovery following ischemic stroke". Dani is continuing her education in medicine.