研究领域

Neurosciences

Gene Therapy for Spinal Cord Injury. After an injury, the adult spinal cord fails to regenerate and damage at cervical levels are particularly devastating as they may result in quadriplegia. One aspect of my research is to use adenoviral vectors carrying the gene sequence for brain-derived neurotrophic factor (BDNF) to up-regulate levels of BDNF into spinal cord motor neurons.We have developed a rat model of rubrospinal tract (RST) transection. While retaining the ability to reach, these rats are no longer capable to rotate the paw during the grasping action, a motor sequence called the arpeggio movement. The loss of arpeggio movement in our rat model is a unique behavioural read-out that we aim to reverse by BDNF gene therapy. The neural basis of skilled reaching. Rats are trained to reach for sugar pellets, a paradigm called "Skilled Reaching". Reaching is filmed when performance has reached an asymptote and the rats are then subjected to selective lesions along the motor pathways. After recovery from the surgical procedure, the rats are tested and filmed again. Performance before and after the surgery is compared using a frame-by-frame analysis of the movies to see the effects of such lesions to their reaching performance. Muscle-motor neuron topography. My team is also currently investigating the relationship between the muscles of the hind- and forelimb and the spinal cord motor neuron columns that innervate them in rats and mice using retrograde neuronal tracers. Nerve excitability. We have recently developed a new research project that focuses on the changes in excitability that occur over time after small spinal cord injury. Changes in nerve excitability in RST rats are measured with threshold tracking techniques. These techniques provide information on axonal biophysical properties, specifically regarding the behaviour of various ion channels, pumps and exchangers that are involved in impulse conduction. The aim of this project is also to measure the benefits of BDNF gene therapy on axon conductance after an injury. The fate of motor neurons below a spinal cord injury. Whether motor neurons die after a spinal cord injury is still a matter of debate. Furthermore, the process by which spinal cord motor neurons could die, i.e. whether they go down the apoptotic or the necrotic pathway, or perhaps both, is undefined. The aim of this project is to explore the possibility that RST lesions trigger apoptotic or necrotic motor neuron death and to measure the benefits of AdBDNF gene therapy on the viability of these motor neurons. Changes in mRNA levels of BDNF and TrkB receptor after RST transection. Are endogenous levels of BDNF and TrkB (the receptor for BDNF) down-regulated by a RST transection? Can we restore levels of BDNF and TrkB mRNA? After a RST transection, motor neurons are collected with a laser capture microdissection (LMD) system and mRNA for BDNF is isolated with state-of-the-art techniques.

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Mehta P; Premkumar B; Morris R, 2016, 'Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Mi', Neuroscience Letters, vol. 627, pp. 132 - 138, http://dx.doi.org/10.1016/j.neulet.2016.05.063 Tosolini AP; Morris R, 2016, 'Viral-mediated gene therapy for spinal cord injury (SCI) from a translational neuroanatomical perspective', Neural Regeneration Research, vol. 11, no. 5, pp. 743 - 744, http://dx.doi.org/10.4103/1673-5374.182698 Morris R; Whishaw IQ, 2016, 'A proposal for a rat model of spinal cord injury featuring the rubrospinal tract and its contributions to locomotion and skilled hand movement', Frontiers in Neuroscience, vol. 10, no. JAN, http://dx.doi.org/10.3389/fnins.2016.00005 Mohan R; Tosolini AP; Morris R, 2015, 'Segmental distribution of the motor neuron columns that supply the rat hindlimb: A muscle/motor neuron tract-tracing analysis targeting the motor end plates', Neuroscience, vol. 307, pp. 98 - 108, http://dx.doi.org/10.1016/j.neuroscience.2015.08.030 Mohan R; Tosolini AP; Morris R, 2015, 'Intramuscular injections along the motor end plates: A minimally invasive approach to shuttle tracers directly into motor neurons', Journal of Visualized Experiments, vol. 2015, no. 101, http://dx.doi.org/10.3791/52846 Morris R; Vallester KK; Newton SS; Kearsley AP; Whishaw IQ, 2015, 'The differential contributions of the parvocellular and the magnocellular subdivisions of the red nucleus to skilled reaching in the rat', Neuroscience, vol. 295, pp. 48 - 57, http://dx.doi.org/10.1016/j.neuroscience.2015.03.027 Morris R; Whishaw IQ, 2015, 'Arm and hand movement: Current knowledge and future perspective', Frontiers in Neurology, vol. 6, no. FEB, http://dx.doi.org/10.3389/fneur.2015.00019 Mohan R; Tosolini AP; Morris R, 2014, 'Targeting the motor end plates in the mouse hindlimb gives access to a greater number of spinal cord motor neurons: An approach to maximize retrograde transport', Neuroscience, vol. 274, pp. 318 - 330, http://dx.doi.org/10.1016/j.neuroscience.2014.05.045 Pinyon JL; Tadros SF; Froud KE; Wong ACY; Tompson IT; Crawford EN; Ko M; Morris R; Klugmann M; Housley GD, 2014, 'Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear', Science Translational Medicine, vol. 6, no. 233, http://dx.doi.org/10.1126/scitranslmed.3008177 Tosolini AP; Mohan R; Morris R, 2013, 'Targeting the full length of the motor end plate regions in the mouse forelimb increases the uptake of Fluoro-Gold into corresponding spinal cord motor neurons', Frontiers in Neurology, vol. 4 MAY, http://dx.doi.org/10.3389/fneur.2013.00058 Tosolini AP; Morris R, 2012, 'Spatial characterization of the motor neuron columns supplying the rat forelimb', Neuroscience, vol. 200, pp. 19 - 30, http://dx.doi.org/10.1016/j.neuroscience.2011.10.054 Morris R; Tosolini AP; Goldstein JD; Whishaw IQ, 2011, 'Impaired arpeggio movement in skilled reaching by rubrospinal tract lesions in the rat: A behavioral/anatomical fractionation', Journal of Neurotrauma, vol. 28, no. 12, pp. 2439 - 2451, http://dx.doi.org/10.1089/neu.2010.1708 Wu A; Lauschke JL; Morris R; Waite PME, 2009, 'Characterization of rat forepaw function in two models of cervical dorsal root injury', Journal of Neurotrauma, vol. 26, no. 1, pp. 17 - 29, http://dx.doi.org/10.1089/neu.2008.0675 Morris R; Morgan BS; Lewis TM; Pierce KD; Pisano A; Schofield PR, 2004, 'In vivo somatic delivery of plasmid DNA and retrograde transport to obtain cell-specific gene expression in the central nervous system', Journal of Neurochemistry, vol. 90, no. 6, pp. 1445 - 1452, http://dx.doi.org/10.1111/j.1471-4159.2004.02612.x Pierce KD; Handford CA; Morris R; Vafa B; Dennis JA; Healy PJ; Schofield PR, 2001, 'A nonsense mutation in the α1 subunit of the inhibitory glycine receptor associated with bovine myoclonus', Molecular and Cellular Neuroscience, vol. 17, no. 2, pp. 354 - 363, http://dx.doi.org/10.1006/mcne.2000.0934 Morris R; Paxinos G; Petrides M, 2000, 'Architectonic analysis of the human retrosplenial cortex', Journal of Comparative Neurology, vol. 421, no. 1, pp. 14 - 28, http://dx.doi.org/10.1002/(SICI)1096-9861(20000522)421:1<14::AID-CNE2>3.0.CO;2-S Morris R; Petrides M; Pandya DN, 1999, 'Architecture and connections of retrosplenial area 30 in the rhesus monkey (macaca mulatta)', European Journal of Neuroscience, vol. 11, no. 7, pp. 2506 - 2518, http://dx.doi.org/10.1046/j.1460-9568.1999.00672.x Morris R; Pandya DN; Petrides M, 1999, 'Fiber system linking the mid-dorsolateral frontal cortex with the retrosplenial]presubicular region in the rhesus monkey', Journal of Comparative Neurology, vol. 407, no. 2, pp. 183 - 192, http://dx.doi.org/10.1002/(SICI)1096-9861(19990503)407:2<183::AID-CNE3>3.0.CO;2-N Morris R; Frey S; Kasambira T; Petrides M, 1999, 'Ibotenic acid lesions of the basolateral, but not the central, amygdala interfere with conditioned taste aversion: Evidence from a combined behavioral and anatomical tract-tracing investigation', Behavioral Neuroscience, vol. 113, no. 2, pp. 291 - 302, http://dx.doi.org/10.1037/0735-7044.113.2.291 Frey S; Morris R; Petrides M, 1997, 'A neuroanatomical method to assess the integrity of fibers of passage following ibotenate-induced damage to the central nervous system', Neuroscience Research, vol. 28, no. 3, pp. 285 - 288, http://dx.doi.org/10.1016/S0168-0102(97)00048-5