Dr Jonathan McDearmid

McDearmid.gifAssociate Professor

Adrian Building, Room 337a

Telephone:

internal:  3913
external: +44 (0)116 2523913
fax:        +44 (0)116 2523330

Email:  jrm33@le.ac.uk

Teaching

  • BS-2076 Evolutionary and Developmental Biology (contributor)
  • BS-2077 Neurobiology and Animal Behaviour (contributor)
  • BS-2066 Behavioural Neurobiology (contributor)
  • BS3077 Developmental Neurobiology (course convenor)

Administration

  • MIBTP Director for the University of Leicester

Publications

  • Jay M, De Faveri F and McDearmid J (2015) Firing Dynamics and Modulatory Actions of Supraspinal Dopaminergic Neurons During Zebrafish Locomotor Behaviour. Current Biology. 25 1-10.
  • Ramesh T, Shaw P and McDearmid J (2014) A zebrafish model exemplifies the long preclinical period of motor neuron disease. J Neurol Neurosurg Psychiatry DOI:10.1136/jnnp-2014-308288
  • Jay M, Bradley S & McDearmid J (2014) Effects of Nitric Oxide on Neuromuscluar Properties of Developing Zebrafish Embryos. PLOS One DOI: 10.1371/journal.pone.0086930
  • Kabashi E, El Oussini H, Bercier V, Gros-Louis F, Valdmanis PN, McDearmid J, Mejier IA, Dion PA, Dupre N, Hollinger D, Sinniger J, Dirrig-Grosch S, Camu W, Meininger V, Loeffler JP, René F, Drapeau P, Rouleau GA, Dupuis L. (2013) Investigating the contribution of VAPB/ALS8 loss of function in amyotrophic lateral sclerosis.Hum Mol Genet. 2013 Mar 3.
  • Huaxia Tong & Jonathan R McDearmid (2012) Pacemaker and Plateau Potentials Shape Output of a Developing Locomotor Network. Current Biology. 22(24) 2285-93
  • Alexander McGown, Jonathan R McDearmid, Niki Panagiotaki, Huaxia Tong, Sufana Al Mashhadi, Natasha Redhead, Alison Lyon, Christine E. Beattie, Pamela J. Shaw and Tennore M. Ramesh (2012) Early interneuron dysfunction in ALS: Insights from a mutant sod1 zebrafish model. Annals of Neurology. 73(2):246-58
  • Bradley S, Tossell K, Lockley R, McDearmid JR (2010) Nitric oxide synthase regulates morphogenesis of zebrafish spinal cord motoneurons. Journal of Neuroscience. 30(50):16818-31.
  • Reynolds A, McDearmid JR, Lachance S, De Marco P, Merello E, Capra V, Gros P, Drapeau P, Kibar Z (2010) VANGL1 rare variants associated with neural tube defects affect convergent extension in zebrafish. Mech Dev. 127(7-8):385-92.
  • Gros-Louis F, Kriz J, Kabashi E, McDearmid J, Millecamps S, Urushitani M, Lin L, Dion P, Zhu Q, Drapeau P, Julien JP, Rouleau GA. (2008) Als2 mRNA splicing variants detected in KO mice rescue severe motor dysfunction phenotype in Als2 knock-down zebrafish. Hum Mol Genet. 17(17):2691-702.
  • McDearmid JR, Liao MJ and Drapeau P (2006) Glycine receptors signal interneuron differentiation during spinal network development. Proceeding of the National Academy of Sciences USA. 103(25): 9679-9684
  • McDearmid JR and Drapeau P (2006) Rhythmic motor activity evoked by NMDA in the spinal zebrafish larvae. Journal of Neurophysiology. 95: 401-417
  • Merrywest SD, McDearmid JR, Kjaerulff O, Kiehn O and Sillar KT (2003) Mechanisms underlying the noradrenergic modulation of longitudinal coordination during swimming in Xenopus laevis tadpoles. European Journal of Neuroscience, 17(5): 1013-22
  • Drapeau P, Saint-Amant L, Buss RR, Chong M, McDearmid JR and Brustein E (2003) Development of the locomotor network in zebrafish. Progress in Neurobiology, 68(2):85-111

Research

  • mechanisms regulating the assembly and maturation of the zebrafish locomotor circuitry
  • research involves a range of electrophysiological, behavioural, histological and molecular methods

Locomotor development, function and disease

Our research is focused on motor network development, function and disease. To do this, we study circuits controlling swimming behaviour in the zebrafish, a small cyprinid native to the streams of India and Bangladesh. Zebrafish are an excellent model for such studies because they generate rapidly developing, optically transparent embryos that are fertilized outside the mother.

Furthermore, a range of powerful genetic techniques are available that allow investigators to manipulate the expression of zebrafish genes, thus facilitating the identification and study of genes important for nervous system function.

Like all vertebrates, the nerve cell networks coordinating zebrafish motor activity are contained within the spinal cord. Moreover, the networks that drive zebrafish motor behaviour are similar to those of mammals, so we can use this organism to ask broad questions about how vertebrate motor circuits are assembled and how they function to generate purposeful outputs.

In addition, the zebrafish can be used to model a range of human diseases that affect motor performance, helping us to better understand the causes and consequences of these disorders.

Our laboratory uses patch clamp electrophysiology, molecular genetic, imaging and behavioural methods to study motor network development, function and disease.

Presently our group focuses on three main research areas:

Neuronal signalling molecules that influence motor circuit maturation

A major focus of our research has been to identify the role neurochemicals play in shaping maturation of motor networks. For example, we have recently shown that nitric oxide (NO), a small messenger molecule, is synthesised are released by a population of developing zebrafish spinal cord neurons. Using pharmacological and molecular methods we have manipulated NO signalling during development so that the impact on motor network maturation could be assessed. We have found that NO has an important role in regulating the number of contacts formed between motoneurons, nerve cells that communicate with muscle cells, and their target muscles.

Subsequently, using in vivo electrophysiology we have shown that NO also influences the formation and physiological maturation of motoneuron-muscle connections. Our findings shed light on the relevance of this signalling molecule to vertebrate motor maturation and suggest that developmental defects on NO signalling may contribute to developmental maladies affecting nerve-muscle signalling.

Developmental transitions in motor output

All developing motor networks must undergo major transitions in motor output before mature behaviours can be generated. However, the cellular processes underpinning the switch from immature to mature behaviour is not fully understood. A major transition that is common to all vertebrates is the switch from nascent, cursory forms of spontaneous network activity to more complex, coordinated forms of adult-like behaviour.

In zebrafish, this transition is characterised by the switch from embryonic 'coiling' behaviour to adult-like 'swimming' behaviour. We have found that coiling behaviour is underpinned by a sub-class of spinal cord neuron that exhibit 'pacemaker'-like activity, meaning these cells generate intrinsic patterns of rhythmic depolarising activity that drive motor network output.

Subsequently, during the transition to swimming, these neurons loose pacemaker capability and adopt a new form of firing activity that is characterised by plateau-like depolarisations. Our findings have provided important new insights into the organisation and maturation of motor networks and has allowed us to determine how early forms of motor output are generated.

Motor network disease

We also use the zebrafish as a model to study the causes and physiological changes associated with motoneuron disease, an untreatable orphan disease that causes degeneration of motoneurons.

At present, there is no known cure for this disorder and life expectancy after diagnosis is two to three years. We are collaborating with a number of research groups to investigate the molecular signalling pathways and pathophysiological aspects of this disease.

Most recently, we have helped to demonstrate that motoneuron disease causes widespread stress within populations of spinal cord inhibitory interneurons which reduces inhibitory inputs onto motoneurons. We are now investigating whether this defect contributes to disease onset.

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Contact

Department of Neuroscience, Psychology and Behaviour
University of Leicester
University Road
Leicester
LE1 7RH

T: +44 (0)116 252 2922
E: npbenquiries@le.ac.uk

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