Bruce E. McKay

Bruce E. McKay, PhD
MSc Laurentian University 2001
PhD Neuroscience University of Calgary 2006
PhD Dissertation: Control of Purkinje cell spike output

Current Gig:
Assistant Professor
Department of Psychology
Wilfrid Laurier University
75 University Ave West Waterloo
Ontario N2L 3C5 bmckay@wlu.ca

Training 1999 BSc Behavioural Neuroscience Laurentian University Sudbury Ontario	2001 MSc Behavioural Neuroscience Laurentian University Sudbury Ontario Supervisor: M. Persinger	2002- 2006 PhD Neuroscience University of Calgary Calgary Alberta Supervisor: R.W. Turner
Special Courses 2002 Cold Spring Harbour Physiological Approaches to Ion Channel Biology	Soc. Neuroscience Short Courses 2003 Mouse Behavioral Phenotyping 2004 Visualizing large-scale activity in the brain: optical and electrical signals	2005 Cold Spring Harbour Biology of Memory

Awards
MSc
NSERC-PGSA Studentship
Ontario Graduate Scholarship
Governor General Award

PhD
NSERC-PGSB Studentship
Dean's Research Excellence Award
Keith Cooper Award (2)
FGS Exellence in Research Award (2)
Teaching Assistantship

AHFMR Studentship
Killam Trust PhD Studentship
CIHR Canada Graduate Scholarship
Alberta Steinhauer Award
JB Hyne Research Innovation Award
NSERC Postdoctoral Fellowship
AHFMR Postdoctoral Fellowship

   Research Focus: The ionic basis of electrical activity in mammalian cerebellar Purkinje cells
   Approach:    Electrophysiology in vitro, pharmacology, immunocytochemistry, molecular biology
   Preparations: In vitro slice preparations, expression systems (HEK, CHO), behavioral pharmacology

Below are short summaries of my projects published from the Turner lab.

Model - Cerebellar Purkinje cells
I use dual soma-dendritic patch clamp recording techniques and immunocytochemistry to examine how voltage-gated potassium and calcium-dependent currents shape the firing properties of cerebellar Purkinje cells. The contribution of specific ion channels to somatic or dendritic activity are analyzed using whole-cell or outside-out patch clamp recordings from somatic or dendritic regions, together with local ejection of ion channel toxins.

Biotin is endogenously expressed in select brain regions
Biotin is a vitamin with a high affinity for avidin compounds that is used in all immuno-cytochemical reactions that rely on the ABC technique to determine the distribution of antigens. A key assumption is that biotin is not expressed in the tissues examined. We show that biotin is endogenously expressed at high levels in specific brain regions, leading to potential false-positive results unless care is taken to prevent labeling of endogenous biotin. PDF

Kv3 potassium channels regulate Purkinje cell burst discharge
Using whole-cell and outside-out recordings I show that Purkinje cells express high threshold Kv3 potassium channels. These channels prove to have a key role in repolarizing both sodium and calcium spikes in Purkinje cells and set several parameters of burst discharge. The primary outcome is to prevent calcium spikes from inactivating somatic spike discharge, which would effectively block spike output to deep cerebellar nuclei. PDF

Kv1 K+ channels regulate the climbing fiber EPSP

Kv1 potassium channels optimize rebound discharge in deep cerebellar neurons
In this study we examined the role of low threshold Kv1 K+ channels in controlling Purkinje cell discharge and its effect on the activity of postsynaptic deep cerebellar neurons. I show that Kv1 channels lower Na+ spike frequency and raise the threshold for Ca2+ spike discharge. When these spike patterns are applied as stimulus templates to Purkinje cell axons, we found that Kv1 channels lower Purkinje cell output frequency to a range that optimizes rebound discharge in deep cerebellar neurons. PDF

Purkinje cell at P90 stage of development

Development of Purkinje cell morphology and spike output
In this study we examined the physiology and morphology of rat cerebellar Purkinje cells recorded in the in vitro slice preparation from P0 to P90 animals. I show that Na+ and Ca2+ spike components of PC output change dramatically during development, with a distinct transition near P9. Development of Ca2+-dependent spike responses and the trimodal pattern of discharge inherent to PCs in vitro are closely linked to the appearance and expansion of the PC dendritic arbor. Rated in top 10 for downloaded manuscripts J Physiol. website Sept. 05. PDF

Rebound burst discharge in deep cerebellar neurons

T-type Ca2+ channel isoforms correlate with distinct burst phenotypes
In this study we determined the distribution of the three isoforms of T-type currents (Cav3.1, 3.2, 3.3) in rat cerebellar neurons, revealing a greater range of expression and contribution to rebound discharge than realized. Moreover, a distinct expession pattern for Cav3 isoforms in deep cerebellar nuclear neurons is shown to correlate to either a strong or weak rebound discharge capability. See Molineux et al. (2006) PDF

The effects of temperature on Cav3.x T-type calcium channels
In this study we compared the properties of T-type calcium channel isoforms recorded in HEK cells at room temperature vs 37 degrees C to facilitate comparisons to native neuronal currents. The work revealed substantial effects of temperature on the rates of channel activation and inactivation, and in some cases isoform-specific shifts in voltage-dependent properties.
See Iftinca et al. 2006 PDF

Cav3 immunolabel in cortical pyramidal dendrites

T-type calcium channel isoforms differentially distribute to soma and dendrites
In this study we used antibodies specific to each of the Cav3 family of T-type calcium channels (Cav3.1, 3.2, 3.3) to compare the distribution of these isoforms over the soma-dendritic axis of cells in neocortex, hippocampus, thalamus and cerebellum. We find a general subcellular pattern for the three isoforms between cells, with Cav3.3 preferentially targeted to both somatic and dendritic compartments. See McKay et al. 2006. PDF

CF discharge converts Purkinje cell output

Climbing fiber input regulates intrinsic properties of Purkinje cells
In this study we show that climbing fiber input activated at physiological frequencies blocks an intrinsic trimodal pattern inherent to Purkinje cells studied in vitro, restoring tonic Na+ spike discharge similar to that found in vivo. Moreover, all the effects of direct climbing fiber stimulation were reproduced by simulating climbing fiber input with an injected EPSC in the presence of synaptic blockers, emphasizing a key role for the postsynaptic complex spike depolarization in determining Purkinje cell activity. See McKay et al. 2007.

Select Peer-reviewed Publications

Engbers, J.D.T.*, Anderson, D.*, Asmara, H., Rehak, R., Mehaffey, W.H., Hameed, S., McKay, B.E., Kruskic, M., Zamponi, G.W. and Turner, R.W. (2011) Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells. PNAS, In Press. * Shared first authors.

McKay, B.E., Engbers, J.D.T., Mehaffey, W.H., Gordon, G., Molineux, M.L., Bains, J. and Turner, R.W. (2007) Climbing fiber discharge regulates cerebellar functions by controlling the intrinsic characteristics of Purkinje cell output. J. Neurophysiology 97: 2590-2604. PDF

McKay, B.E., McRory, J.E., Molineux, M.L., Hamid, J., Snutch, T.P., Zamponi, G.W. and Turner, R.W. (2006) Cav3 T-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons. European J. Neuroscience 24: 2581-2594. PDF

Iftinca, M., McKay, B.E., Snutch, T.P., McRory, J.E., Turner, R.W. and Zamponi, G.W. (2006) Temperature dependence of T-type calcium channel gating. Neuroscience 142(4):1031-1042. PDF

Molineux, M.L., McRory, J.E., McKay, B.E., Hamid, J., Mehaffey, W.H., Snutch, T.P., Zamponi, G.W. and Turner, R.W. (2006) Specific T-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons. PNAS 103(14): 5555-5560. PDF Supplementary data

McKay, B.E. and Turner, Ray W. (2005) Physiological and morphological development of the rat cerebellar Purkinje cell. J. Physiology (Lond.) 567(Pt 3): 829-50. PDF

McKay, B.E. , Molineux, M.L., Mehaffey, W.H. and Turner, Ray W. (2005) Kv1 potassium channels control Purkinje cell output to facilitate post-synaptic rebound discharge in deep cerebellar neurons. J. Neuroscience 25(6): 1481-1492. PDF

McKay, B.E. and Turner, R.W. (2004). Kv3 potassium channels regulate burst output in rat cerebellar Purkinje cells. Eur. J. Neuroscience 20 (3): 729-739. PDF

McKay, B.E., Molineux, M.L., and Turner, R.W. (2004) Biotin is endogenously expressed in select regions of the rat central nervous system. J. Comparative Neurology 473(1): 86-96. PDF

Invited Chapters:

McKay, B.E., Molineux, M.L., and Turner, R.W. (2007) Endogenous expression of biotin in central neurons. Methods in Molecular Biology , vol. 418: Avidin-Biotin Interactions. R. J. McMahon (ed) Methods Mol Biol. © Humana Press Inc., Totowa, NJ 418:111-128.

McKay BE and Turner RW. (2006) Developing insights in Purkinje cell maturation. Developing insights in Purkinje cell maturation. Physiology News, J. Physiol. (Lond.). No 63. PDF

Key Abstracts

McKay BE, Rashid AJ, Dunn RJ and Turner RW. The localization of Kv3.3 potassium channels in murine central neurons. Alberta Neuroscience Mtg, Canmore 2002.

McKay BE and Turner RW Highly TEA-sensitive K+ currents regulate spike discharge of mature rat cerebellar Purkinje cells. Ann Proc Soc Neurosci 2003.

Turner RW, Molineux ML and McKay BE. Endogenous biotin in the rat CNS - Implications for false-positive avidin-biotin reactions. Ann Proc Soc Neurosci 2003.

McKay BE, Molineux ML, and Turner, RW. Endogenous biotin in the rat CNS - potential false-positive (strept)avidin-biotin interactions in the rat brain. Alberta Neuroscience Mtg, Canmore 2003.

McKay BE and Turner RW Kv1 K+ channels regulate excitability of rat cerebellar Purkinje cells and climbing fibers. Ann Proc Soc Neurosci 2004.

Molineux ML, McRory JE, McKay BE, Mehaffey WH, Hamid J, Snutch TP, Zamponi GW, and Turner RW. Specific Cav3 T-type calcium channel isoforms are associated with bursting and nonbursting cerebellar neurons. Proc. Soc. Neurosci. 2005.

McKay BE and Turner RW. Physiolgical and morphological development of the rat cerebellar Purkinje cell. Proc. Soc. Neurosci. 2005.

McKay BE, Engbers JDT, Mehaffey WH, Gordon GRJ, Molineux ML, Bains JS and Turner RW. Climbing fibre control of Purkinje cell spike output. Can Assoc Neurosci 2007 [Can J. Neurol. Sci., 34 (Supplement 3): S87].

Hurlock EC, McMahon A, McKay BE, Turner RW and Joho RH. Purkinje cell-restricted restoration of Kv3.3 channel function rescues complex spikes and motor coordination in Kv3.3-mutant mice. Proc. Soc. Neurosci. 2007.

Engbers, J.D.T., McKay, B.E., Rehak, R., Zamponi, G.W. and Turner, R.W. T-type calcium channels are activated by synaptic inputs to trigger an AHP in cerebellar Purkinje cells. Can. Assoc. Neurosci. 2008.

Turner, R.W., Engbers, J.D.T., McKay, B.E., Rehak, R., and Zamponi, G.W. T-type calcium channel control of Purkinje cell excitability. T-type Calcium Channel Workshop, Kiev 2008.

Engbers, J.D.T., Anderson, D., Rehak, R., Mehaffey, W.H., McKay, B.E., Zamponi, G.W. and Turner, R.W. T-type/IK channel signalling complex modulates summation of parallel fiber inputs in cerebellar Purkinje cells. Can. Assoc. Neurosci. 2010.

Engbers, J.D.T., Anderson, D., Rehak, R., Mehaffey, W.H., McKay, B.E., Zamponi, G.W. and Turner, R.W. IKCa channels establish a high pass filter for parallel fiber input in cerebellar Purkinje cells. Gordon Conference, Cerebellum in Health and Disease, New London, NH, 2011.

Engbers, J.D.T., Anderson, D., Rehak, R., Asmara, H., Mehaffey, W.H., Hameed, S., McKay, B.E., Kruskic, M., Zamponi, G.W., Turner, R.W. IKCa-Cav3 complex reduces temporal summation of parallel fiber input in cerebellar Purkinje cells. IBRO World Congress of Neuroscience, Florence, Italy, 2011.

Engbers, J.D.T., Anderson, D., Rehak, R., Mehaffey, W.H., McKay, B.E., Kruskic, M., Zamponi, G.W., Turner, R.W. IKCa-Cav3 complex creates a high pass filter for parallel fiber input in cerebellar Purkinje cells. Comp. Neurosci., Stockholm, Sweden, 2011. Prize, Student Poster Presentation.

Full Curriculum Vitae Please email Bruce McKay for latest CV.

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