Indiana University Bloomington

Neuroscience
Neuroscience
Kenneth Mackie

Kenneth Mackie

Brown University, ScB, Engineering, 1980
Yale University, MD, 1984
Post-doctoral fellowship, 1984-1986, Advisor—Paul Greengard
Internship (Internal Medicine) Yale University, 1986-1987
Residency (Anesthesiology) University of Washington, 1987-1990
Post-doctoral fellowship, 1990-1992, Advisor—Bertil Hille

Email address: kmackie(at)indiana.edu

Research Interests

Areas of study/research topics:
Regulation of CB1 cannabinoid receptor signaling
Regulation of endocannabinoid production
Role of endocannabinoids in synaptic plasticity
Novel cannabinoid receptors

The Mackie lab examines the role and function of the endocannabinoid system by using a combination of electrophysiological, imaging, biochemical and immunological approaches. The endocannabinoid system is comprised of cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes that regulate the production and degradation of endocannabinoids. ?9THC, the principal psychoactive component of cannabis, interacts with this system to produce the classic effects of cannabis intoxication. In addition, this system is widely involved in multiple physiologically important processes including memory, motivation, movement, analgesia, and emesis. Through our studies, we hope to better understand the implications of social and therapeutic use of drugs that influence this fascinating system.

Representative Publications

Keimpema E., Tortoriello G., Alpar A., Capsoni S., Arisi I., Calvigioni D., Hu S.S., Cattaneo A., Doherty P., Mackie K., & Harkany T. (2013). Nerve growth factor scales endocannabinoid signaling by regulating monoacylglycerol lipase turnover in developing cholinergic neurons. PNAS USA 110(5), 1935-1940.

Shonesy B.C., Wang X., Rose K.L., Ramikie T.S., Cavener V.S., Rentz T., Baucum A.J. 2nd., Jalan-Sakrikar N., Mackie K., Winder D.G., Patel S., & Colbran R.J. (2013). CaMKII regulates diacylglycerol lipase-alpha and striatal endocannabinoid signaling. Nat. Neurosci., 16(4), 456-463.

Jung K.M., Sepers M., Henstridge C.M., Lassalle O., Neuhofer D., Martin H., Ginger M., Frick A., DiPatrizio N.V., Mackie K., Katona I., Piomelli D., & Manzoni O.J. (2012). Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile x syndrome. Nat. Commun., 3, 1080.

Atwood B.K., Straiker A., & Mackie K. (2012). CB2 cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons. Neuropharmacology, 63(4), 514-523.

Straiker A., Wager-Miller J., & Mackie K. (2012). The CB1 cannabinoid receptor C-terminus regulates receptor desensitization in autaptic hippocampal neurones. Br. J. Pharmacol., 165(8), 2652-2659.

Straiker A., Wager-Miller J., Hutchens J., & Mackie K. (2012). Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones. Br. J. Pharmacol., 165(8), 2660-2671.

Pickel V.M., Shobin E.T., Lane D.A., & Mackie K. (2012). Cannabinoid-1 receptors in the mouse ventral pallidum are targeted to axonal profiles expressing functionally opposed opioid peptides and contacting N-acylphosphatidylethanolamine-hydrolyzing phospholipase D terminals. Neuroscience, 227, 10-21.

Atwood B.K., Wager-Miller J., Haskins C., Straiker A., & Mackie K. (2012). Functional selectivity in CB2 cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB2 ligands. Mol. Pharmacol., 81(2), 250-263.

Straiker A., Wager-Miller J., Hu S.S., Blankman J.L., Cravatt B.F., & Mackie K. (2011). COX-2 and fatty acid amide hydrolase can regulate the time course of depolarization-induced suppression of excitation. Br. J. Pharmacol. 164(6), 1672-1683.

Ho Y.C., Lee H.J., Tung L.W., Liao Y.Y., Fu S.Y., Teng S.F., Liao H.T., Mackie K., & Chiou L.C. (2011). Activation of orexin 1 receptors in the periaqueductal gray of male rats leads to antinociception via retrograde endocannabinoid (2-arachidonoylglycerol)-induced disinhibition. J. Neurosci., 31(41), 14600-14610.

Keimpema E., Barbaras K., Morozov Y.M., Tortoriello G., Torii M., Cameron G., Elphick M.R., Egertova M., Yanagawa Y., Watanabe M., Mackie K., & Harkany T. (2010). Differential subcellular recruitment of monoacylglycerol lipase generates spatial specificity of 2-arachidonoyl glycerol signaling during axonal pathfinding. J. Neurosci., 30, 13992-14007.

Atwood B.K. & Mackie K. (2010). CB2 in neurons:  A receptor with an identity crisis. Br. J. Pharmacol., 160, 467-479

Wu C.-S., Zhu J., Wager-Miller J., Wang S., O’Leary D., Monory K., Lutz B., Mackie K., & Lu H.-C. (2010). Requirement of cannabinoid CB1 receptor in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections. Eur. J. Neurosci., 32, 693-706.

Catterall W.A. & Mackie K. (2010). Local Anesthetics.  in Goodman and Gilman's:  The Pharmacological Basis of Therapeutics.  (Ed. J.G. Hardman, L.E. Limbard, P.B. Molinoff, T.W. Rall, and R.W. Ruddon) McGraw Hill.

Atwood B.K., Huffman J., Straiker A., & Mackie K. (2010). JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious CB1 receptor agonist. Br. J. Pharmacol., 160, 585-593.

Straiker A., Hu S.S., Long J., Arnold A., Wager-Miller J., Cravatt B., & Mackie K. (2009). Monoacyl glycerol lipase (MGL) limits the duration of endocannabinoid-mediated depolarization-induced suppression of excitation (DSE) in autaptic hippocampal neurons. Mol. Pharmacol., 76, 1220-1227.

Kellogg R., Mackie K., & Straiker A. (2009). Cannabinoid CB1 receptor-dependent long-term depression in autaptic excitatory neurons. J. Neurophysiol., 102, 1160-1171.

Lauckner J.E., Jensen J.B., Chen H.-Y., Lu H.-C., Hille B., & Mackie K. (2008). GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc. Natl. Acad. Sci. USA, 105, 2699-2704.

Daigle T.L, Kwok M.L., & Mackie K. (2008). Regulation of CB1 receptor internalization by a promiscuous phosphorylation-dependent mechanism. J. Neurochem., 106, 70-82.

Daigle T.L., Kearn C.S., & Mackie K. (2008). Rapid CB1 cannabinoid receptor desensitization defines the time course of ERK1/2 MAP kinase signaling. Neuropharmacology 54, 36-44.

Berghuis P., Rajnicek A.M., Morozov Y.M., Ross R.A., Mulder J., Monory K., Marsicano G., Lutz B., Matteoli M., Canty A., Yanagawa Y., Rakic P., Mackie K., & Harkany T. (2007). Hardwiring the brain: Endocannabinoids control axon guidance. Science, 316, 1212-1216.