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.

Claire Meehan info

 

 

 

 

In our lab we use advanced electrophysiological and anatomical techniques to investigate the excitability and connectivity of spinal neurons in vivo. We explore both normal spinal motor control and how changes in neuronal excitability play a role in the pathophysiology of various injury and disease states affecting the motor system.

Research interests

Amyotrophic Lateral Sclerosis (ALS): ALS is a neurodegenerative disease preferentially affecting upper and lower motor neurons, which currently has no cure. The underlying pathophysiology of the disease is unclear, but there is considerable evidence that dysfunctional 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 motor neurons, and how environmental factors correlated with ALS incidence in human populations impact disease onset and progression.

Frontotemporal Dementia (FTD): FTD accounts for approximately 1/20 of all dementias, and frequently concurrent with ALS. Affecting preferentially the frontal and temporal lobes, this results in behavior and personality changes and well as difficulties in language and memory. Around 50% of ALS patients show signs of FTD. We are investigating the role of neuronal excitability changes both at the single-cell and network level underlying such behavioral changes.

Spinal cord injury: Spinal cord trauma results not only in the loss of function, but also gain of function, below the site of injury. Gain of function, including chronic pain, autonomic dysfunction, and spasticity severely impairs quality of life in spinal cord injury patients. 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 the plasticity of the neuronal regions where action potentials are generated and renewed: the axon initial segment and the nodes of Ranvier, respectively. Our previous work has shown that these regions are highly plastic, and current work focuses on investigating the role of this plasticity in various injury and disease states.

 

 

 

 

 

 

 

 

Jørgensen H.S, Jensen DB, Dimintiyanova KP, Bonnevie VB, Hedegaard A, Lehnhoff J, Moldovan M, Grondahl L & Meehan CF. Increased axon initial segment length results in increased Na+ currents in spinal motoneurones at symptom onset in the G127X SOD1 mouse model of Amyotrophic Lateral Sclerosis. Neuroscience. 2021 Aug 1;468:247-264

Jensen DB, Kadlekova M, Allodi  I & C.F. Meehan. Spinal motoneurones are intrinsically more responsive in the adult G93A SOD1 mouse model of Amyotrophic Lateral Sclerosis. J Physiol. 2020 Oct;598(19):4385-4403.

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.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

We are extremely grateful to have received funding from the following foundations for our current research:

  • The Independent Research Fund Denmark
  • The Lundbeck Foundation
  • The Danish Association of Neuroscience

 

 

 

 

 

 

 

 

CLAIRE FRANCESCA MEEHAN

Education

Feb 2005: PhD Neurological Studies:  Institute of Neurology (University College London), UK
August 2000: MSc Clinical Neuroscience: Institute of Neurology (University College London), UK

Current and most recent positions

From 2013:        Associate Professor (Lektor). Dept of Neuroscience, University of Copenhagen
2013-2013         Assistant Professor. Dept. Neuroscience & Pharmacology, University of Copenhagen
2007-2012         Postdoctoral Research Fellow (Coordinator of own Lab), University of Copenhagen
2004-2007         Postdoctoral Fellow Department of Physiology. Queens University, Canada

Academic awards/honours and funding (Past 10 years)

2022: Independent Research Fund Denmark (IRFD): project grant 2,500,000 DKK
2022: Lundbeck Experiment Project Grant: 2,000,000 DK
2021: Dagmar Marshalls Fond: 100,000 DK
2020: Jascha Fonden Project Grant: 300,000 DKK
2018: Independent Research Fund Denmark (IRFD): project grant 2,500,000 DKK
2017: Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis' Project Grant: 760, 000 DKK
2011-2016: Lundbeck Foundation: 2 Project grants: 3,600,000 DKK in total
2010-2011: Marie Curie Research Fellowship (European Union FP7 program), 1.518.440 DKK
Also 4 scholar stipends (Novo Nordisk, IRFD, DSFN, approx 60,000-100,000 DKK each)                                           

Teaching

Bachelor Medicine: Semester 2 and 3 Courses (CNS Course leader, lecturer, practical exercises and examiner),
Masters in Human Biology Lecturer, practical exercise instructor
Masters in Neuroscience: Lecturer, practical exercise instructor and examiner
Study Board member (Neuroscience, Immunology and Human Biology Masters)

 

 

  • Professor Jyoti Watters (University of Wisconsin-Madison): Microglia-Motoneurone signalling
  • Senior Researcher Sanne Simone Kaalund (Research Laboratory for Stereology and Neuroscience, Bispebjerg University Hospital): Stereology in ALS-FTD models
  • Associate Professor Rune Berg (University of Copenhagen): in vivo calcium imaging in ALS
  • Associate Prof. Mihai Moldovan/Prof. Christian Krarup (University of Copenhagen /Rigshospital): Peripheral nerve excitability in neuromuscular disorders
  • Associate Professor Jacob Wienecke (University of Copenhagen): Axonal excitability following spinal cord injury
  • Associate Professor Sandra Breum Andersen (Section of Microbiology. Globe Institute, University of Copenhagen): The microbiome in ALS
  • Associate Professor Tim Dyrby (DTU/Hvidøre Hospital): Axon diameter in ALS
  • Professor Gareth Miles (University of Saint Andrews, UK): Axo-axonic control of motoneurone excitability

 

 

 

 

Bak AN, Djukic S, Kadlekova M, Braustein T, Jensen DB, and Meehan CF
Cytoplasmic TDP-43 accumulation drives changes in C-bouton number and size in a mouse model of sporadic ALS.
bioRxiv 2022.05.20.492885; doi: https://doi.org/10.1101/2022.05.20.492885

Goltash S, Jensen MH, Dimintiyanova KP, Jensen DB, Lehnhoff J, Moldovan M & Meehan CF. Homeostatic changes maintain the gain control of spinal motoneurones during aging in C57BL/6J mice
bioRxiv 2022.05.19.492717; doi: https://doi.org/10.1101/2022.05.19.492717

Jensen DB, Kadlecova M, Allodi I, Meehan CF.
Response to Letter to Editor on the article Jensen DB, Kadlecova M, Allodi I, Meehan CF (2020). J Physiol. 2021 Sep;599(17):4233-4236.

C Krarup, K Dimintiyanova, D Jensen, C Meehan, M Moldovan
A Progressive Increase in Threshold Variability Impacts Mscanfit Motor Unit Number Estimation in the SOD1G93A Mice and Patients with Amyotrophic Lateral Sclerosis (2713)
Neurology 2021, 96 (15 Supplement)

CF Meehan, EH Utoft, C Parsons, VJ Hall, M Bendixen, I Vogel, KP Gill.
Impact of the first COVID-19 lockdown on scientific productivity and workload in Denmark: a gender analysis. SocArXiv 2021 (https://osf.io/preprints/socarxiv/7uvt3/)

Cowley KC, Lane MA, Meehan CF, Rank MM, Stecina K
Editorial: Propriospinal Neurons: Essential Elements in Locomotion, Autonomic Function and Plasticity After Spinal Cord Injury and Disease. Front Cell Neurosci. 2021 May 20;15:695424.

Jørgensen H.S, Jensen DB, Dimintiyanova KP, Bonnevie VB, Hedegaard A, Lehnhoff J, Moldovan M, Grondahl L & Meehan CF. Increased axon initial segment length results in increased Na+ currents in spinal motoneurones at symptom onset in the G127X SOD1 mouse model of Amyotrophic Lateral Sclerosis. Neuroscience. 2021 Aug 1;468:247-264

Jensen DB, Kadlekova M, Allodi  I & C.F. Meehan. Spinal motoneurones are intrinsically more responsive in the adult G93A SOD1 mouse model of Amyotrophic Lateral Sclerosis. J Physiol. 2020 Oct;598(19):4385-4403.

Meehan CF, Ford TW & Kirkwood PA. Plasticity of thoracic interneurones rostral to a lateral spinal cord lesion.
Exp Neurol. 2020 Sep;331:113361. doi: 10.1016/j.expneurol.2020.113361.

Christensen NR, De Luca M, Lever MB, Richner M, Hansen AB Jensen KL, Rathje M, Noes-Holt G, Jensen DB, Erlendsson S, Bartling CRO Ammendrup-Johnsen, I, Pedersen SE, Schönauer M,  Nissen KB, Midtgaard SR, Teilum K, Arleth L, Sørensen AT, Bach A, Strømgaard K, Meehan CF, Vægter CB, Gether U, Madsen KL
A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain. EMBO Mol Med. 2020 Jun 8;12(6):e11248. doi: 10.15252/emmm.201911248

Bonnevie VS, Dimintiyanova KP, Hedegaard AH, Lehnhoff J, Grøndahl L, Moldovan M, Meehan CF
Shorter axon initial segments do not cause repetitive firing impairments in the adult presymptomatic G127X SOD-1 Amyotrophic Lateral Sclerosis mouse.
Sci Rep. 2020 Jan 28;10(1):1280.

Jensen DB, Klingenberg S, Dimintiyanova K, Wienecke J, Meehan CF
Intramuscular Botulinum toxin A injections induce central changes to axon initial segments and cholinergic boutons on spinal motoneurones in rats.
Sci Rep. 2020 Jan 21;10(1):893

Bendixen M, Meehan C, Hall VJ, Vogel I.
Denmark's exemplary gender balance trips up in science.
Nature. 2019 Aug;572(7768):178. Commentary

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.

Peer-reviewed conference proceedings

Lehnhoff, J., Moldovan, M., Hedegaard, A., Grøndahl, L. & Meehan, CF
In vivo intracellular recordings from spinal lumbar motoneurones in P0-deficient mice indicate an activity-dependent axonal conduction failure in otherwise functional motoneurones
Proc Physiol Soc 2014. UK, Vol. 31. PCA079

Ford, T. W., Meehan, CF & Kirkwood, PA
Abdominal and internal intercostal motoneurones are strong synergists for expiration but are not synergists for Group I monosynaptic afferent inputs
Proc Physiol Soc 2014. Vol. 31. PCB066

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

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 Image
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Carly Mickelson Postdoc Meehan Lab Billede af Carly Mickelson
Claire Francesca Meehan Associate Professor Meehan Lab Billede af Claire Francesca Meehan
Hans Hultborn Professor Emeritus Meehan Lab Billede af Hans Hultborn
Mathilde Alfang Master-Student Meehan Lab Billede af Mathilde Alfang
Niels Ulrik Grøndahl Bachelor student Meehan Lab Billede af Niels Ulrik Grøndahl
Sandra Duval Dræby Master-Student Meehan Lab Billede af Sandra Duval Dræby
Viktória Reháková Research Assistant Meehan Lab Billede af Viktória Reháková
Zhenxiang Zhao PhD Student Meehan Lab Billede af Zhenxiang Zhao