Meehan Lab

The main experimental approach of the laboratory has been the use and development of electrophysiological techniques in which the excitability and connectivity of spinal neurones can be investigated in transgenic rodent models in vivo.

Research focus

The main experimental approach of the laboratory has been the use and development of electrophysiological techniques in which the excitability and connectivity of spinal neurones can be investigated in transgenic rodent models in vivo. Using this, we explore both normal spinal motor control and the role of changes in neuronal excitability in the pathophysiology of various injury and disease states affecting the motor system.

We focus mainly on

Amyotrophic Lateral Sclerosis. This is a neurodegenerative disease preferentially affecting upper and lower motor neurons with no current cure. The underlying pathophysiology of the disease is unclear but there is considerable evidence that neuronal excitability plays a role. Using transgenic models of the disease we are exploring the contributions of altered neuronal excitability to the degeneration of the motoneurons.

Spinal cord injury. Spinal cord trauma results not only in the loss of functions controlled by the spinal cord below the injury, but also gains of function. These can serious impair quality of life and include chronic pain, autonomic dysfunction and spasticity. We are exploring the plasticity of neuronal excitability and circuitry following spinal cord injury that underlie these phenomena.

Plasticity of excitable domains of axons: We are interested in plasticity of the action potential generating region of motoneurons- the axon initial segment along with the nodes of Ranvier where action potentials are renewed. We have shown these to be highly plastic structures on spinal motoneurons and are trying to investigate the role that this plays in various injury and disease states.

Key publications

Maglemose R, Hedegaard A, Lehnhoff J, Moldovan M, Grondahl L & Meehan CF. (2017) Potassium channel abnormalities are consistent with early axon degeneration of motor axons in the G127X SOD-1 Mouse Model of Amyotrophic Lateral Sclerosis. Experimental Neurology 2017 Jun;292:154-167
Meehan CF. Mayr KA, Manuel M, Nakanishi ST, & Whelan PLJ. (2017) A protocol for using decerebrate mice to record from spinal cord circuits. Nat Protoc. Apr; 12(4):732-747.
Hedegaard A, Lehnhoff J, Moldovan M, Grøndahl L, Petersen NC, Meehan CF. (2015) Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice. J. Neurophysiol. Aug;114(2):1196-210.
Hultborn H, Zhang M & Meehan CF. (2013) Plateau Potential Properties in Spinal Cord Neurons. Curr Pharm Des.19(24):4357-70.
Meehan CF, Moldovan M, Marklund SL, Graffmo KS, Nielsen JB, Hultborn H. Intrinsic (2010) Properties of Lumbar Motoneurons in the Adult G127insTGGG Superoxide Dismutase-1 Mutant Mouse in Vivo: Evidence for Increased Persistent Inward Currents. Acta Physiol (Oxf). Dec;200(4):361-76.
Meehan CF, Sukiasyan N, Zhang M, Nielsen JB, Hultborn H. (2010) Intrinsic properties of mouse lumbar motoneurons revealed by intracellular recording in vivo. J Neurophysiol. May; 103(5):2599-610.
Meehan CF, Grøndahl L, Nielsen JB, Hultborn H. (2012) Fictive Locomotion in the Adult Decerebrate and Spinal Mouse In Vivo. J Physiol . Jan 15;590(Pt 2):289-300
Meehan CF, MacDermid VE, Montague SJ, Neuber-Hess M, Rose PK. (2011) Dendrite-derived supernumerary axons on adult axotomized motor neurons possess proteins that are essential for the initiation and propagation of action potentials and synaptic vesicle release. J Neurosci. May 4; 31(18):6732-40.

Current funding

Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis Legat.

CV - Claire Meehan

CLAIRE FRANCESCA MEEHAN

Current Position

Associate Professor (Lektor)
Department of Neuroscience
Panum Building 24.4
University of Copenhagen
Denmark

EDUCATION

Feb 2005 Ph.D. Neurological Studies
Institute of Neurology (University College London), UK Supervisor: Dr Peter Kirkwood

August 2000 MSc. Clinical Neuroscience
Institute of Neurology (University College London)/National Hospital for Neurology & Neurosurgery, UK
(Short Project: Human TMS. Supervisor Prof John Rothwell)

CURRENT AND MOST RECENT POSITIONS

Dec 2013 Associate professor (Lektor)
Dept. of Neuroscience, University of Copenhagen, Denmark.

Feb 2013 Assistant professor (Adjunkt)
Dept. of Neuroscience and Pharmacology, University of Copenhagen, Denmark.

2007-2012: Postdoctoral Fellow
(Coordinator Mouse Laboratory, Neural Control of Movement Research Group: Hans Hultborn / Jens Bo Nielsen,
University of Copenhagen, Denmark.

2004 – 2007: Postdoctoral Fellow
Department of Physiology. Laboratory of Dr P Ken Rose, Queens University, Canada

EXTERNAL RESEARCH GRANTS

2018-2021: Independent Research Fund Denmark: Project 1 grant 2,500,000 DKK
Role: Principle investigator

2017-2020 Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis' Project Grant: 760,000 DKK
Role: Principle investigator.

2017-2018 Danish Research Council Pregraduate Scholarship to Sara Klingenberg: 144,000 DKK

2014-2016 Lundbeck Foundation: Project grant: 2,000,000 DKK
Role: Principle investigator.

2011-2013 Lundbeck Foundation: Project grant: 1,600,000 DKK
Role: Principle investigator.

2010-2011 Marie Curie Research Fellowship, 1,518,440 DKK
European Union FP7 program, Brussels, Belgium/EU

2000-2003 Medical Research Council (UK) PhD Studentship

Specific skills

Intracellular recording in adult mice in vivo
Neuroanatomical skills (including tracing, immunohistochemistry and confocal microscopy)
Electrophysiological techniques in humans

MANAGEMENT EXPERIENCE

For the past 8 years I have established, managed and funded an in vivo electrophysiology laboratory in the Department of Neuroscience at The University of Copenhagen.

TEACHING (at University of Copenhagen)

Bachelor Medicine: Semester 2 and 3 Courses:

Kursus I excitable celler (Practicals),
Kursus i centralnervesystemets struktur og funktion (lectures, case studies, EMG practicals and examiner)

Masters in Human Biology:

Course in Neuronal signalling (lectures and practicals in neuroanatomy)
Pharmacology and Toxicology (lectures in local and general anaesthesia)
Advanced Cell Biology/ Molecular Biology and Genetics (Supervisor for theoretical Projects)

SUPERVISIONS OF STUDENTS

2009-2017:
Bachelor Project Students: 10
MSc Students: 6
PhD Students : 1 (as project supervisor) successfully defended, 1 current

COLLABORATIONS

Local:

Ass. Prof. Mihai Moldovan/Prof. Christian Krarup (University of Copenhagen/Rigshospital): Neuronal excitability in transgenic models of motor disorders.
Prof. Ole Kiehn: (co-supervised PhD student from 2017)

National:

Part of a new Danish ALS consortium (including Ass. Prof. Mai Marie Holm and Ass. Prof. Thomas Holm Pedersen, Arhus University and Mihai Moldovan, University of Copenhagen).

International:

Prof. Mahmoud Kiaei (University of Arkansas for Medical Sciences US) Providing the Profilin 1 ALS model.
Prof. Alexander George Rabchevsky (The University of Kentucky College of Medicine. US):

Techniques

Our main methods include in vivo electrophysiology in adult mice including intracellular recording in both anaesthetised and decerebrate models (see Meehan et al 2017, Nature Protocols). This allows us to perform recordings in adult transgenic models of neurological diseases.

We also combine this with neuroanatomical techniques including intracellular labelling, neuronal tracing and immunohistochemistry.

Full publication list

Jensen DB, Stecina K, Wienecke J, Hedegaard A, Sukiasyan N, Hultborn HR, Meehan CF. The Subprimary Range of Firing Is Present in Both Cat and Mouse Spinal Motoneurons and Its Relationship to Force Development Is Similar for the Two Species. J Neurosci. 2018 Nov 7;38(45):9741-9753.

Maglemose R, Hedegaard A, Lehnhoff J, Moldovan M, Grondahl L & Meehan CF. Potassium channel abnormalities are consistent with early axon degeneration of motor axons in the G127X SOD-1 Mouse Model of Amyotrophic Lateral Sclerosis. Exp Neurol. 2017 Jun; 292: 154-167.

Meehan CF. Mayr KA, Manuel M, Nakanishi ST, & Whelan PLJ. A protocol for using decerebrate mice to record from spinal cord circuits. Nat Protoc. 2017 Apr;12(4):732-747.

Ford TW, Anissimova NP, Meehan CF, Kirkwood PA. Functional plasticity in the respiratory drive to thoracic motoneurons in the segment above a chronic lateral spinal cord lesion. J Neurophysiol. 2016 Jan 1;115(1):554-67.

Hedegaard A, Lehnhoff J, Moldovan M, Grøndahl L, Petersen NC, Meehan CF. Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice. J. Neurophysiol. 2015 Aug;114(2):1196-210.

Randsoe T, Meehan CF, Broholm H, Hyldegaard O. Effect of nitric oxide on spinal evoked potentials and survival rate in rats with decompression sickness. J Appl Physiol (1985). 2015 Jan 1;118(1):20-8.

Ford TW, Meehan CF, and Kirkwood PA. Absence of synergy for monosynaptic Group I inputs between abdominal and internal intercostal motoneurons. J Neurophysiol. 2014 Sep 1;112(5):1159-68

Hultborn H, Zhang M & Meehan CF Plateau Potential Properties in Spinal Cord Neurons. Curr Pharm Des. 2013;19(24):4357-70.

Fedirchuk B, Stecina K, Kristensen KK, Zhang M, Meehan CF, Bennett DJ, Hultborn H. Rhythmic activity of feline dorsal and ventral spinocerebellar tract neurons during fictive motor actions. J Neurophysiol. 2013 Jan;109(2):375-88.

Meehan CF, Grøndahl L, Nielsen JB, Hultborn H. Fictive Locomotion in the Adult Decerebrate and Spinal Mouse In Vivo. J Physiol. 2012 Jan 15;590(Pt 2):289-300

Meehan CF, MacDermid VE, Montague SJ, Neuber-Hess M, Rose PK. Dendrite-derived supernumerary axons on adult axotomized motor neurons possess proteins that are essential for the initiation and propagation of action potentials and synaptic vesicle release. J Neurosci. 2011 May 4;31(18):6732-40.

Saywell SA, Ford TW, Meehan CF, Todd A, and Kirkwood PA. Electrophysiological and morphological characterization of propriospinal interneurons in the thoracic spinal cord. Journal Neurophysiology. 2011 Feb;105(2):806-26.

Geertsen SS, Stecina K, Meehan CF, Nielsen JB, Hultborn H. Reciprocal Ia inhibition contributes to motoneuronal hyperpolarisation during the inactive phase of locomotion and scratching in the cat. J Physiol. 2011 Jan 1;589(Pt 1):119-34.

Meehan CF, Moldovan M, Marklund SL, Graffmo KS, Nielsen JB, Hultborn H. Intrinsic Properties of Lumbar Motoneurons in the Adult G127insTGGG Superoxide Dismutase-1 Mutant Mouse in Vivo: Evidence for Increased Persistent Inward Currents. Acta Physiol (Oxf). 2010 Dec;200(4):361-76.

Meehan CF, Sukiasyan N, Zhang M, Nielsen JB, Hultborn H. Intrinsic properties of mouse lumbar motoneurons revealed by intracellular recording in vivo. J Neurophysiol. 2010 May;103(5):2599-610.

Fenrich KK, Skelton N, Macdermid VE, Meehan CF, Armstrong S, Neuber-Hess MS, Rose PK. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy. J Comp Neurol. 2007 Jun 20;502(6):1079-97.

Saywell SA, Anissimova NP, Ford TW, Meehan CF, Kirkwood PA. The respiratory drive to thoracic motoneurons in the cat and its relation to the connections from expiratory bulbospinal neurones. J Physiol. 2007 Mar 15;579(Pt 3):765-82.

Meehan CF, Ford TW, Road JD, Donga R, Saywell SA, Anissimova NP, Kirkwood PA. Rostrocaudal distribution of motoneurons and variation in ventral horn area within a segment of the feline thoracic spinal cord. J Comp Neurol. 2004 May 3;472(3):281-91.

Refereed proceedings

Hedegaard A, Lehnhoff J, Moldovan M, Groendahl L, Meehan, CF Post activation depression of the Ia EPSP in motoneurons is reduced in both aged mice and in the G127X SOD1 model of Amyotrophic lateral sclerosis. Physiology 2014 (London, UK),Proc Physiol Soc 31(2014) PCA070

Lehnhoff J, Moldovan M, Hedegaard A, L. Groendahl L, Meehan, CF In vivo intracellular recordings from spinal lumbar motoneurons in P0-deficient mice indicate an activity-dependent axonal conduction failure in otherwise functional motoneurons Physiology 2014 (London, UK), Proc Physiol Soc 31(2014) PCA079

Azam A, Wienecke J, Groendahl L, Meehan, CF Mechanisms of hypereflexia following spinal cord injury: The role of the axon initial segment. Physiology 2014 (London, UK), Proc Physiol Soc 31(2014) PCB062

Ford TW, Meehan CF, Kirkwood PA Abdominal and internal intercostal motoneurons are strong synergists for expiration but are not synergists for Group I monosynaptic afferent inputs Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB066

Non peer reviewed publications

Chapters:

Meehan C. & Hultborn. H. Gener og bevægelse (Genetics and Movement). In “Hjernen i bevægelse” (the Brain and Movement). 2009 HjerneForum (in Danish)

Nicolas Caesar Petersen, Claire Meehan, Hans Hultborn, Tue Hvass Petersen og Jens Bo Nielsen Chapter 11:Nervesystemets Udvikling og Børns Motorik. In “Fra Tanke til Handling - Bevægelsens Neurobiologi”. 2016 Hjerneforum (in Danish)

Lab members

Name	Title	Job responsibilities

Claire Francesca Meehan	Associate Professor	Meehan Lab
Dennis Bo Jensen	PhD Student	Meehan lab
Hans Hultborn	Part-time Lecturer	Meehan lab
Helena Hedegaard Udsen	Student	Meehan Lab
Kristina Petrova Dimintiyanova	PhD Student	Meehan Lab
Sif Møbjerg Jørgensen	Bachelor student	Meehan Lab
Tanja Djukic	Master-Student	Meehan Lab