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Division of Neurodegenerative Disorders Visiting Speaker - Dr. Sean Mulligan http://www.medicine.usask.ca/physiology/people/faculty-members/sean-mulligan/sean-mulligan.html

DATE: Friday, June 17th, 011 TIME: 12:00 Noon LOCATION: Theatre A

Biosketch: Dr. Sean Mulligan Assistant Professor, Department of Physiology Neural Systems & Plasticity Research Group, College of Medicine, University of Saskatchewan Postdoctoral Fellow (Psychiatry) Faculty of Medicine, University of British Columbia Ph.D. (Neuroscience) Faculty of Medicine, University of Calgary M.Sc. (Biology/Neurobiology) Simon Fraser University B.Sc. (Kinesiology/Anatomy & Physiology) Simon Fraser University

Teaching Interests Neuroscience Cellular and Systems Level Physiology

Research Interests Pain sensitivity within the skull is restricted to the intracranial meninges, the system of membranes that envelops the brain. Afferent thinly myelinated A��-fibres and unmyelinated C-fibres that originate from the trigeminal ganglion densely innervate the meninges, in particular the cranial dura mater. It is widely recognized that activation or sensitization of these dural nociceptive afferents is responsible for the genesis of migraine headaches. However, any details of the pathophysiological mechanisms involved are largely speculative and remain to be discovered. Identification of the underlying mechanisms of activation of dural nociceptors may have important implications for understanding and mitigating the pathogenesis of migraine headaches. We have developed a novel en bloc dural-skull preparation that allows us for the first time to apply optical imaging techniques to directly study with high resolution the free nerve endings and terminals of the nociceptive fibres that terminate in the dura mater. The objective of our research is to gain insight into the neurophysiology of peripheral pain activation to better understand the pathophysiological processes that occur during migraine headache. It is our hope that this will lead to new peripheral drug targets and offer additional therapeutic treatments for this devastating illness.

Laboratory Techniques We are primarily an optical imaging laboratory that uses both two-photon laser scanning imaging as well as widefield epifluorescence microscopy. Microscopes are configured for both microfluorometric and transmitted light imaging using photomultiplier tube or high sensitivity EMCCD camera based detection. We combine optical imaging of calcium signaling selectively within individual terminals with electrophysiological stimulation, pharmacological manipulations, and UV and two-photon photolysis of caged compounds.

Selected Publications

Papers in refereed journals: Zampronio, A. R., Kuzmiski, J. B., Florence, C.M., Mulligan, S. J. and Pittman, Q. J. Opposing actions of endothelin-1 on glutamatergic transmission onto vasopressin and oxytocin neurons in the supraoptic nucleus. Journal of Neuroscience (in press)

Hines, D.J., Hines, R.M., Mulligan, S.J., and Macvicar, B.A. Microglia processes block the spread of damage in the brain and require functional chloride channels. Glia. 2009 Nov 15;57(15):1610-8.

Umeshappa C.S., Huang, H., Xie, Y., Wei, Y., Mulligan, S.J., Deng, Y., and Xiang, J. CD4+ Th-APC with acquired peptide/MHC class I and II complexes stimulate type 1 helper CD4+ and central memory CD8+ T cell responses. Journal of Immunology Vol 182 pp 193-206 (2009).

Pittman, Q. P and Mulligan, S.J. Dendritic Vasopressin Release: Reducing the Flow Makes Blood Vessels Grow. Endocrinology Vol 149(9) pp 4276-4278 (2008).

Kisilevsky, A.E., Mulligan, S.J., Christophe, A., Iftinca, M.C., Varela, D., Tai, C., Chen, L., Hameed, S., Hamid, J., MacVicar, B.A. and Zamponi, G.W. D1 and D2 dopamine receptors interact directly with N-type calcium channels and differentially regulate channel activity. Neuron Vol 58 pp 557-570 (2008).

Gordon, G.R., Mulligan, S. J. and MacVicar, B.A. Astrocyte control of the cerebrovasculature. Glia Vol 55 pp 1214-1221 (Cover Image) (2007).

Mulligan, S.J. and MacVicar, B. A. VRACs CARVe a path for novel mechanisms of communication in the CNS. Science STKE Vol 2006/357 pe42 (2006).

Mulligan, S.J. and MacVicar, B. A. Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature Vol 431/7005 pp 195-199 (2004).

Mulligan, S.J., Davison, I. and Delaney, K.R. Mitral cell presynaptic Ca2+ influx and synaptic transmission in frog amygdala. Neuroscience Vol 104/1 pp 137-151 (2001).

Book Chapters:

Florence, C.M. and Mulligan, S.J. Two-Photon Laser Scanning Microscopy: Imaging Astrocyte Calcium Signalling in the Brain Slice Preparation. In Neuromethods series, edited by Walz, W. and Doucette, R., Humana Press (2009).

Gordon G.R.J., MacVicar, B.A., and Mulligan, S.J. Glia Control of Blood Flow. In The New Encyclopedia of Neuroscience, edited by Squire, L.R., Oxford:Academic Press (2009).

Mulligan, S.J. and MacVicar, B. A. Two-Photon Fluorescence Microscopy: Basic Principles, Advantages and Risks. In Modern Research and Educational Topics in Microscopy, edited by A. M��ndez-Vilas, J. D��az, Formatex (2007).

MacVicar, B. A. and Mulligan, S.J. Intrinsic Optical Signal Imaging in Brain slices. In Imaging in Neuroscience and Development: A Laboratory Manual, edited by Yuste, R. and Konnerth, A., Cold Spring Harbor Laboratory Press. (2005).

Mulligan, S.J. and MacVicar, B. A. Monitoring Intracellular Ca2+ in Brain Slices with Fluorescent Indicators. In Voltage-Gated Calcium Channels, edited by Zamponi, G.W., Landes Bioscience (2005).

Kelly Jorundson

Winnipeg Chapter Society for Neuroscience R4046 �C 351 Tach�� Avenue Winnipeg, MB R2H 2A6 CANADA

Tel: 204.235.3939 7Fax: 204.237.4092 Email: wcsn@sbrc.ca Website: www.sfn-manitoba.ca