Professor David Maxwell
- Professor of Neuroanatomy (Centre for Neuroscience)
- Associate (School of Life Sciences)
Regulation of synaptic transmission in the spinal cord by monoaminergic systems and spinal interneurons. Spinal mechanisms of neuropathic pain. Organisation of spinal interneurons in reflex pathways.
Descending and segmental control of primary afferent transmission in the spinal cord.
The contribution of spinal mechanisms to neuropathic pain.
Organisation of neurotransmitters and receptors in the dorsal and ventral horn.
Monoamines and neuronal transmission in the spinal cord
Dr D.J. Maxwell.
My present research interests are focused on various aspects of spinal cord circuitry. I use an approach which combines electrophysiological and morphological techniques. Much of this work is performed in collaboration with other laboratories in Glasgow and Sweden. I am a member of The Spinal Cord Research Group , in Glasgow. The work is funded by the Wellcome Trust and the Robertson Trust.
(1) Synaptic bases of monoaminergic inhibition of spinal interneurons
A confocal microscopic image of a spinal interneuron.
Hyperactivity of nerve cells in the spinal cord contributes to the exaggerated reflexes which occur in spasticity. Pathways containing monoamine transmitters pass from the brain to the spinal cord and control the activity of spinal neurons but the basis of this control is poorly understood. Interneurons in the spinal cord are selectively controlled by these descending fibres and it is these neurons which probably become hyperactive in spastic patients, since drugs which mimic the actions of monoamines depress their activity and also reduce spasticity. The aim of this project is to investigate the neuronal circuitry underlying these phenomena by filling various classes of physiologically characterized spinal interneurons with fluorescent dyes or enzymes and then labelling the fibres descending from the brain with antibodies that recognise monoamine neurotransmitters. Contacts between descending fibres and interneurons are investigated with confocal laser scanning microscopy and electron microscopy. It is anticipated that this approach will provide a better basis for the development of new drugs for the treatment of spasticity. Reference:Maxwell, D.J., Jankowska, E.J., Dolk, S., Riddell, J.S., Yin, X.-K. and Dahlström, A. (1995) Ultrastructural and confocal microscope studies of neurotransmitters in boutons which contact interneurons in pathways from muscle afferents. Brain Research Association Abstracts, 12, 27.4.
(2) Control of transmission through the spinocerebellar tract
A group of neurons which form a component of the spinocerebellar tract, is located in the dorsal horn of the lumbar spinal cord. This pathway receives information from muscle afferents and cutaneous afferents and, in addition to supplying the cerebellum with information, has a role in the conscious perception of limb position. Although functional properties and morphology of cells belonging the pathway have been described in some detail, knowledge about the organization and neurochemistry of synaptic connections of these neurons is still sparse. The principal objective of this project is to elucidate control mechanisms which influence transmission through the this pathway. We are currently investigating immunocytochemical properties of axons originating from various regions of the brain and their synaptic relationships with identified spinocerebellar tract neurons. References:Jankowska, E., Maxwell, D.J., Dolk, S., Krutki, P. Belichenko, P.V. and Dahlström, A. (1995) Contacts between serotoninergic fibres and dorsal horn spinocerebellar tract neurones in the cat and rat; a confocal microscopic study. Neuroscience, 67,477-487. Maxwell, D.J. and Jankowska, E. (1996) Synaptic relations between serotonin-immunoreactive axons and dorsal horn spinocerebellar tract cells in the cat spinal cord. Neuroscience, 70, 247-253.
(3) Organization of terminations of primary afferent fibres in the spinal grey matter.
The principal aim of this project is to investigate the various ways in which information coming into the spinal cord via primary afferent fibres is modified at the first synapse in the cord. Such knowledge is important if we are to improve our understanding of pain mechanisms and abnormalities of posture and movement. Primary afferents originating from muscles and skin are stained by various means (e.g. by intra-axonal labelling with enzymes passed through microelectrodes) and their terminations are examined with light and electron microscopy. Immunocytochemistry is combined with this approach to investigate the chemical nature of structures which are pre- and post-synaptic to primary afferent axons.
References:Maxwell, D. J. and Réthelyi, M. (1987) Ultrastructure and synaptic connections of cutaneous afferent fibres in the spinal cord. Trends in Neuroscience, 10, 117-123. Maxwell, D.J., Christie, W.M., Short, A.D. and Brown, A.G. (1990) Direct observations of synapses between GABA- immunoreactive boutons and muscle afferent terminals in lamina VI of the cat's spinal cord. Brain Research 530, 215-222. Figure : An electrophysiological record from a primary afferent axon (A). The axon was labelled with an enzyme and its fine ramifications were viewed with a light microscope (B). The same axon was studied with an electron microscope (*) and it formed synapses (arrow) with other neurons (C).
1. Maxwell, D.J., Todd,A.J. and Kerr, R. (1995) Colocalization of glycine and GABA in synapses on spinomedullary neurons. Brain Research 690, 127-132.
2. Maxwell, D.J. and Jankowska, E. (1996) Synaptic relations between serotonin-immunoreactive axons and dorsal horn spinocerebellar tract cells in the cat spinal cord. Neuroscience, 70, 247-253. 3. McGonigle, D.J., Maxwell, D.J., Shehab, S.A.S. and Kerr,R. Evidence for the presence of neurokinin-1 receptors on dorsal horn spinocerebellar tract cells in the rat. Brain Research, (1996) 742, 1-9.
4. Maxwell, L. Maxwell, D.J., Neilson, M. and Kerr, R. A confocal microscopic survey of serotoninergic axons in the lumbar spinal cord of the rat: colocalization with glutamate decarboxylase and neuropeptides. Neuroscience (1996) 75: 471-480
5. Maxwell, D.J., Kerr, R., Jankowska, E. and Riddell, J.S. Synaptic connections of dorsal horn group II interneurons: synapses formed with the interneurons and by their axon collaterals. J.Comp. Neurol. (1997) 380: 51-69
6. Jankowska E., Maxwell, D.J. Dolk, S. and Dahlström, A. A confocal and electron microscopic study of contacts between 5-HT fibres and feline dorsal horn interneurons in pathways from muscle afferents J.Comp. Neurol. (1997) 387, 430-438
7. Pollock, R., Kerr, R. and Maxwell, D.J. An immunocyochemical investigation of the relationship between substance P and the neurokinin-1 receptor in the lateral horn of the rat thoracic spinal cord. Brain Res. (1997) 777, 22-30
8. Spike, R.C., Kerr, R., Maxwell, D.J. and Todd, A.J. GluR1 and GluR2/3 subunits of the AMPA-type glutamate receptor are associated with particular types of neuron in laminae I-III of the spinal dorsal horn of the rat, Eur. J. Neurosci. (1998) 10,324-333.
Grants and Awards listed are those received whilst working with the University of Glasgow.
- Contribution of Spinal Commissural Circuits to Upper Limb Movements
Biotechnology and Biological Sciences Research Council
2017 - 2020
- Selection and generation of limb movements by a combination of multifunctional and specialized spinal interneurons
National Science Foundation
2014 - 2018
- Pre-motor neuronal networks , from connectivity to function
Biotechnology and Biological Sciences Research Council
2013 - 2017
- Corticospinal reorganisation after experimental stroke.
2012 - 2013
- Neuroscience: Organisation and neurochemical properties of intersegmental interneurons in the lumbar enlargement of the adult rat (in press)
The Carnegie Trust for the Universities of Scotland
2010 - 2011
- Confocal microscopic studies in Neuroscience
2010 - 2013
- A quantitative description of glycinergic circuits in the ventral horn of the lumbar spinal cord.
2009 - 2012
- Chemical and ultrastructural characterization of the caudal most spinal cord
Hungarian Ministry of Education
2003 - 2006
- The actions of group II interneurones in spinal cord circuitry controlling locomotion
2003 - 2007
- Confocal microscopic studies in the spinal cord
2002 - 2005
- An Investigation of Spinal Cord Mechanisms Underlying Neuropathic Pain in Nerve Injury Models in the Rat
2000 - 2006
Invited International Presentations
- 2006: London, England - Physiological Society Symposium - Descending control as a determinent of the pain experience: sensory, autonomic and motor aspects.
- 2004: Glasgow, Scotland - Organiser and Chair, Physiological Society Symoposium - Genetic and Molecular Approaches to Investigate Spinal Cord Circuitry
- 2004: Pecs, Hungary - Plenary lecturer, Hungarian Society for Nuroscience
- 2003: Cambridge, England - British Psychopharmacological Society workshop - Immunocytochemical techniques for the identification of receptors
Professional Learned Society
- 1998 - present: Anatomical Society of Great Britain and Ireland - Member
- 1998 - present: Society for Neuroscience - Member
- 1992 - present: British Neuroscience Association - Member
- 1984 - present: Physiological Society - Member