Ph.D. Massachusetts Institute of Technology
Phone: (631) 632-8632
Fax: (631) 632-6661
Life Sciences Building
Office: Room 532
Lab: Room 526
Lorne Mendell was awarded a B.Sc. degree in Mathematics and Physics from McGill University in 1961. In 1965, he received a Ph.D. in Neurophysiology from M.I.T. He was on the faculty of Duke University Medical Center from 1968 to 1980, and joined Stony Brook University in 1980. He served as chair of the Department of Neurobiology and Behavior from 1986 to 2006 and is currently Distinguished Professor of Neurobiology and Behavior. From 1983-89 he was Editor-in-Chief of the Journal of Neurophysiology, and he currently serves on its Editorial Board. He was on the Editorial Board of the Journal of Neuroscience from 1984 to 1989. In 1991-1992 he was President of the Association of Neuroscience Departments and Programs. In 1996 to 1997 he was Treasurer of the Society for Neuroscience and from 1997 to 1998 served as its President. He is presently Chair of the Spinal Cord Injury Research Board of the State of New York as well as a Director of the Craig H. Neilsen Foundation. His research interests focus on neuroplasticity of the mammalian spinal cord.
My laboratory has long been interested in functional effects of neurotrophins in neonatal and adult mammals. For many years this interest was focused on the role of neurotrophins, particularly nerve growth factor (NGF), in inflammatory pain. Another aspect of this research was concerned with the sensitizing effect of Brain Derived Neurotrophic Factor (BDNF) on synaptic transmission from nociceptors onto their synaptic target in the superficial dorsal horn. BDNF is upregulated in nociceptors during inflammation and its release into the dorsal horn sensitizes transmission in nociceptive pathways.
More recently we have been studying the role of a third neurotrophin (NT-3) in modifying the synapse involved in transmission between stretch receptors and motoneurons. This work has prompted us to investigate the development of NMDA receptors on motoneurons since the acute effects of NT-3 on AMPA receptor- mediated glutamatergic transmission requires functional NMDA receptors. We have shown that NMDA receptors in motoneurons undergo a postnatal decrease in function as a result of a postnatal decline in expression of a regulatory subunit (NR2D) with a consequent decrease in the sensitizing effect of NT-3 at this synapse. Reintroducing NR2D resurrects NMDA receptor- mediated transmission on motoneurons with recovery of the ability of NT-3 to influence synaptic transmission at this synapse. These studies are carried out using HSV viruses engineered to contain the gene for NR2D and fibroblasts engineered to secrete NT-3.
We are now also studying the effect of NT-3 in modifying the function of neural pathways that survive after spinal cord injuries. In one case we are examining the blockade of information flow that occurs on the intact side of the spinal cord after hemisection of the other side. We are using combinations of agents including NT-3 in attempts to relieve this blockade which appears to be due at least in part to a loss of myelination in fibers of the spinal cord white matter across from the hemisection.
In other experiments we are examining changes in neural circuitry that could account for the finding that step training of neonatally spinal transected rats increases their ability to step on a treadmill. We find changes in the properties of motoneurons and in the magnitude of the stretch reflex that correlate with the recovery of stepping behavior after training. Since such training also enhances the level of NT-3 in the spinal cord, we are investigating whether artificially enhancing spinal NT-3 levels improves stepping behavior after neonatal transection in the absence of training. We inject AAV viruses engineered to contain the NT-3 gene into limb muscles to enhance NT-3 levels in the spinal cord. The resulting cellular and synaptic changes bear some resemblance to those observed after step training, but our preliminary data indicate some important differences. Currently we are examining the effects of BDNF on these cells and circuits with one aim being an effort to extend these studies to interneurons.
Our experiments in spinal cord injury are in collaboration with the International Research Consortium on Spinal Cord Injury established and funded by the Christopher and Dana Reeve Foundation. Our research is also funded by NIH.
- Honors, Awards & Leadership
- Laboratory Personnel
- Mendell LM, Constructing and deconstructing the gate theory of pain. Pain. 2014 55(2): 210-6.
- Petruska, JC, Kitay, B, Boyce, VS, Kaspar, B, Pearse, D, Gage, FH, Mendell, LM (In Press) Intramuscular AAV delivery of NT-3 alters synaptic transmission to motoneurons in adult rats. Eur. J. Neurosci.
- Hunanyan A, Garcia-Alias G, Levine JM, Fawcett J, Mendell LM and Arvanian VL (2010) Role of chondroitin sulfate proteoglycans (CSPGs) in axonal conduction in mammalian spinal cord. J. Neurosci. 30: 7761-7769. (pdf)
- Shanthanelson, M. and Mendell, LM (2010) Differential NR2B- subunit expression at dorsal root and ventrolateral funiculus synapses on lumbar motoneurons of neonatal rat. Neuroscience 166: 730–737. (pdf)
- Shanthanelson M, Arvanian VL, Mendell LM. (2009) Input-specific plasticity of N-methyl-d-aspartate receptor-mediated synaptic responses in neonatal rat motoneurons. Eur J Neurosci. 29: 2125-36. (pdf)
- Arvanian VL, Schnell L, Lou L, Golshani R, Hunanyan A, Ghosh A, Pearse DD, Robinson JK, Schwab ME, Fawcett JW, Mendell LM. (2009) Chronic spinal hemisection in rats induces a progressive decline in transmission in uninjured fibers to motoneurons. Exp Neurol. 216(2):471-80. (pdf)
- Petruska JC and Mendell LM (2008) Nerve Growth Factor. In: LR Squire, Ed. Encyclopedia of Neuroscience. Vol. 6 P. 71-78, Elsevier. (pdf)
- Petruska JC, Ichiyama RM, Crown ED, Tansey KE, Roy RR Edgerton VR and Mendell LM (2007) Changes in motoneuron properties and synaptic inputs related to step training following spinal cord transection in rats. J. Neuroscience 27: 4460- 4471 (pdf)
- Arvanian VL, Bowers WJ, Anderson AJ, Horner PJ,
Federoff HJ and Mendell LM (2006) Combined delivery of neurotrophin-3
and NMDA receptors 2D subunit strengthens synaptic transmission in
contused and staggered double hemisected spinal cord of neonatal rat Exp. Neurol. 197: 347- 352.
- Levine JM and Mendell LM (2005) Trophic factors and their influence on regeneration. In: Textbook of Neural Repair and Regeneration. Ed: M. Selzer, S. Clarke, L.G. Cohen, P.W. Duncan and F.H. Gage. Cambridge University Press.
- Arvanian VL, Bowers WJ, Petruska JC, Manuzon H, Narrow WC, Motin V, Federoff HJ and Mendell LM (2004) Viral delivery of NR2D subunits reduces Mg2+ block of NMDA receptor and restores NT-3-induced potentiation of AMPA/kainate responses in maturing rat motoneurons J. Neurophysiol. 92: 2394- 2404. (pdf)
- Arvanian VL, Horner PJ, Gage FH and Mendell LM (2003) Chronic Neurotrophin-3 Strengthens Synaptic Connections to Motoneurons in the Neonatal Rat. J. Neurosci. 23: 8706-8712. (pdf)
- 1983-89 Editor-in-Chief, Journal of Neurophysiology
- 1986-90 Council, Society for Neuroscience
- 1991-92 President, Association of Neuroscience Departments and Programs
- 1996-7 Treasurer, Society for Neuroscience
- 1997-8 President, Society for Neuroscience
- 2007- Chairman, New York State Spinal Cord Injury Research Board
- 2007- Board of Directors, Craig Neilsen Foundation
- Li Liang, Research Scientist
- RESENT LAB MEMBERS
- Victor Arvanian, Research Physiologist, Research Associate Professor, Northport Veterans Affairs Medical Center
- Monicca Shanthanelson, Scientific Writer, InVentiv Communications
- Jeff Petruska, Assistant Professor, Dept of Anatomy and Neurobiology, University of Louisville
- Sandra Garraway, Research Associate, Weill/ Cornell Medical College