Professor Ole Kiehn
Department of Neuroscience
Mærsk Tower, room 07-4-54
Phone: +45 93565963
We study the molecular, cellular, and network diversification of locomotor circuitries in mammals with the goal of providing a unified understanding of the functional organization of neuronal circuits that execute movements.
Professor Ole Kiehn
Department of Neuroscience
Mærsk Tower, room 07-4-54
Phone: +45 93565963
A monumental challenge in neuroscience is to understand the operation of neuronal networks that are linked to execution of specific behaviors. Our lab is meeting this challenge by addressing the organization of neuronal networks that produce movements, the origin of all behaviors.
We study the molecular, cellular, and network diversification of locomotor circuitries in mammals with the goal of providing a unified understanding of the functional organization of neuronal circuits that execute movements. To this end, we apply new physiological and molecular genetic approaches, including optogenetics, RNA-seq, molecular tracing, advanced imaging, and electrophysiology.
We have deciphered the functional organization of spinal circuitries necessary for producing changes in timing and coordination of locomotion, and delineated brainstem circuits involved in gating or context-dependent selection of motor behaviors.
The lab also investigates plasticity in spinal networks and motor neurons following lesions of the spinal cord, with the goal of devising manipulations that may alleviate motor dysfunction following spinal cord injury.
In recent efforts, we also address the role of spinal interneurons in development and progression of amyotrophic lateral sclerosis.
Our work bridges the gap between neuronal circuit organization and behaviour, and has strong translational potential in development of therapies for movement disorders caused by trauma or disease.
Physiological and molecular organization of neuronal networks controlling movements in mammals
Movement takes many forms. Among movements, locomotion is one of the most fundamental—used by all animals and humans for interaction with the surroundings. Locomotion is employed episodically in many daily activities, representing an output measure for integrated brain activity involved in exploring the environment, escaping predators, and searching for food. Its activity also directly influences the state of sensory information processing.
The planning and initiation of locomotion takes place in the brain and brainstem, while the execution—which involves precise timing and coordination—is to a large part accomplished by activity within neuronal networks of the spinal cord itself.
Early work from our lab has revealed aspects of the overall organization of spinal locomotor networks, the implication of cellular properties for rhythmicity, and the nature of neuronal spike coding.
Recent work has focused on the functional organization of key neuronal elements that characterize limbed locomotion in mammals: 1) rhythm generation, 2) coordination of flexors and extensors across the same or different joints in a limb or between limbs, and 3) left/right coordination.
Rhythm generating neurons set tempo within the network, and are an elementary component of all vertebrate locomotor networks. Experiments from our lab using genetically driven expression of light-sensitive channels in excitatory and inhibitory neurons have demonstrated that excitatory neurons in the mammalian spinal cord are both sufficient and necessary for initiation and maintenance of rhythmic locomotor pattern. Using intersectional mouse genetics in combination with electrophysiology, we have identified non-overlapping subpopulations of excitatory neurons in the spinal cord that participate in rhythm generation.
We have also characterized networks involved in left-right coordination, which include commissural interneurons (CINs) whose axons cross the midline, in detail using anatomical, electrophysiological, and targeted genetic ablation techniques for molecularly defined subpopulations of CINs.
These studies have converged on a common organizational principle for circuits controlling left-right alternation in mammals, which consists of a modular organization for left-right alternating gaits (walk and trot) and synchronous gaits (gallop/bound). Moreover, we have addressed the organization of circuits controlling flexor-extensor coordination. We are now addressing the functional integration of these diverse circuit elements using both in vitro and in vivo studies.
In a general scheme of motor control, we study how spinal locomotor circuits are activated and controlled by descending command signals. Decision-making signals to locomote are conveyed from the brain to locomotor regions in the midbrain. The locomotor regions in the midbrain include the mesencephalic locomotor region (MLR)—a complex structure—that in turn is thought to activate neurons in the reticular formation (RF) in the lower brainstem, which project to locomotor networks in the spinal cord. In the first optogenetics experiments in the mammalian locomotor system, we provided direct evidence that glutamatergic neurons in the lower brainstem can provide a ‘go’- signal sufficient to activate spinal locomotor networks.
We have now implemented in vivo optogenetic and chemogenetic approaches to probe the involvement of locomotor promoting and locomotor arresting areas in the brainstem, and further explore how these brainstem circuits are selected by upstream circuitries. These experiments have defined ‘start’ neurons in the midbrain, confined to the cuneiform nucleus and pedunculopontine nucleus, which cooperate to set locomotor speed and context-dependent selection of locomotor gate.
We have also defined ‘stop’ neurons in nucleus gigantocellularis that arrest ongoing locomotion.
In future studies we will use Parkinson disease models to probe the role of different motor structures in development and encoding of disease-induced gait disturbances.
Cellular mechanism underlying spasticity after spinal cord injury
Severe muscle spasticity develops as a consequence of spinal cord injury or damage to motor pathways from the brain. We previously found evidence that the pathophysiology of spasticity after spinal cord injury is related to chronic expression of plateau properties in motor neurons. Plateau potentials in vertebrate motor neurons are caused by activation of prolonged sodium/calcium currents, and their expression is dependent on activation of noradrenergic and/or serotoninergic receptors. The normal function of motor neuron plateau potentials seems to be to maintain persistent motor output and amplify synaptic inputs during rhythmic motor activity.
To find possible targets for regulation of plateau potentials after spinal cord injury, we have performed global gene expression profiling from rat motor neurons isolated before or after injury to the cord. These studies have shown that the chronic expression of plateaux may be related to changes in genes coding for the regulatory units for persistent sodium and calcium channels. In ongoing experiments, we are investigating how changes in interneuronal network activity interact with plateaux to generate spasticity using mouse genetic, calcium imaging, and in vivo optogenetic experiments. Our long-term goal is to define new therapies for symptoms associated with spinal cord injury.
Born: September 30 1958. Citizenship: Danish/Swedish.
1985: MD from University of Copenhagen, Denmark.
1990: D.Sci. from University of Copenhagen, Denmark.
2002: Docent, Karolinska Institute, Sweden.
2017-: Professor in Integrative Neuroscience, Department of Neuroscience, University of Copenhagen, Denmark.
2004-: Professor in Neuroscience, Department of Neuroscience, Karolinska Insitute (KI), Sweden.
2001-2004: Group-leader - via international ‘Elite-recruitment’ program at Karolinska Institute, Sweden.
1997-2001: Associate Professor, Department of Physiology, Copenhagen.
1995-2000: Hallas Møller Research Fellow Department of Physiology, Copenhagen.
1991-1995: Group Leader Institute of Neurophysiology, Copenhagen.
1989-1990: Postdoc, Sect. of Neurobiol. and Behavior Cornell University, USA.
1988-1989: Senior Research Associate, Institute of Neurophysiology, Copenhagen.
1985-1988: Junior Research Associate; Institute of Neurophysiology, Copenhagen.
1983-1985: Research Assistant Institute of Neurophysiology, Copenhagen.
2019-: Lundbeck Foundation’s Professorship award.
2017-: Novo Nordic Foundation Laureate program.
2016-: European Research Council advanced grant (second award).
2014: Member of EMBO.
2013: Member of Academia Europea.
2012: Member of the Royal Swedish Academy of Sciences.
2010: Member of the The Royal Danish Academy of Sciences and Letters.
2011-2016: Research Professorship: Torsten and Ragnar Söderberg’s Professorship from the Royal Swedish Academy of Science.
2011-2016: European Research Council advanced grant.
2010-2015: 5 Year Distinguished Professor Award Karolinska Institute.
2004: Recipient of international Schellenberg Prize in spinal cord research.
2001-2006: 5 year recruitment via ‘Elite-recruitment’ program at Karolinska Institute.
1999-2001: PI for Human Frontier Science Program grant.
2001-2010: PI on R01 NIH grant to Kiehn Lab.
1995: Recipient of Hallas Møller Research Fellowship (5 year salary award from Novo Foundation – one/year in biomedicine).
1990: Recipient of Weimann Research Fellowship (5 year salary award).
2019: Co-editor in chief of Current Opinion in Neurobiology.
2017: Member of Steering Committee Department of Neuroscience UCPH.
2017: SAB Dandrite.
2016: Vice Chair Nobel Committee for Physiology or Medicine.
2014-2019: Elected member of the Nobel Committee for Physiology or Medicine.
2011-2013: Affiliated member of the Nobel Committee for Physiology or Medicine.
2008-2028: Elected Member of Nobel Assembly at Karolinska Institute.
2013: Evaluation panel consolidator ERC grant.
2012: Evaluation panel Söderberg’s foundation.
2010: Member of the Scientific Evaluation Committee for ETN in Zurich.
2008 & 2014: Scientific Evaluation Committee for Molecular Physiology of the Brain, Göttingen, Germany.
2006-2010: Member of the steering board of Stockholm Brain Institute.
2011-2015, 2015-: Co-director for StratNeuro at Karolinska Institute.
2003-2011: Deputy Chair at the Department of Neuroscience, Karolinska Institute.
2011-2012: Chair of Program Committee for Federation of European Neuroscience Societies (FENS).
2011-2013: Member of Executive committee for FENS.
2007-2009: Member of program committee for Society for Neuroscience USA.
2009: Member of Program Committee for FENS.
>10 PhD students
(Harris-Warrick/Bruce Johnson, Cornell University; Goulding, Salk Institute; Glover, Oslo University; Del Negro William and Mary, US).
Member of editorial boards: Current Opinion of Neurobiology (2008-), Neural Development (2007-2019), Brain Research Bulletin (2000-), Faculty of 1000 (2004-2009). Journal of Neurophysiology (1996-2012).
Reviewing editor: E-Life (2012-2018), EJN (2015-).
Chief Editor: Current Opinion in Neurobiology (2019-)
Associate Editor: Frontiers in Neuroscience (2011-2016).
Section Editor: Current Opinion of Neurobiology, Motor, 2004 and 2015.
Plenary lectures/Distinguished lectures: FEPS-SIF, Bologna, Italy (2019). Society for Neuroscience, Special Lecture 2017. Plenary Lecture Nordic Neuroscience Meeting, Stockholm 2017. Nichelson Lecture, Rockefeller USA (2016). Riken, Outstanding Research Lecture (2015). Discovery Lecture Karolinska Institutet (2014)/2018. Distinguished Lecture Toronto University – the Tater and Turnbull Lecture (2014). Oxford University, Department of Anatomy and Physiology (2014). Kavli Lecture, Trondheim (2014). Plenary Lecture Winter Conference in Neural Systems (2014). Distinguished Lecture, EPFL Luzanne (2013). Distinguished Lecture, Max Planck Munich (2013). Plenary lecture – motor conference Salk (2013). Plenary Lecture Neuroethology Meeting Baltimore (2012). Distinguished lecture, Department of Neuroscience and Pharmacology Copenhagen (2012). Talk a Fridtjov Nansen 150 year birthday symposium – Norwegian Academy of Sciences (2011). Plenary Lecture, Physiological Society Meeting, St Andrews (2010). Plenary Lecture Scandinavian Physiological Society (2007). Plenary lecture German Zoological Society, Bayreuth, Germany (2005). Gail Memorial Talk, Miami Project to Cure Paralysis International, Miami, USA (2005).
Our lab has developed a broad experimental repertoire, that includes:
These tools provide a solid basis for the sophisticated functional and network studies needed to understand the principal mode of operation of a large-scale mammalian motor circuits.
General papers about Neurobiology
|Carmelo Bellardita||Assistant professor||Kiehn lab|
|Debora Masini||Postdoc||Kiehn Lab|
|Haizea Goñi Erro||PhD student||Kiehn lab|
|Ilary Allodi||Assistant professor||Kiehn lab|
|Ima Mustafic||Senior Mobility Consultant||Kiehn Lab|
|Irene Lisa Vargas||Industrial PhD Student||Kiehn Lab|
|Iryna Vesth-Hansen||Laboratory technician||Kiehn lab|
|Jared Cregg||Postdoc||Kiehn lab|
|Li-Ju Hsu||Postdoc||Kiehn lab|
|Maite Marcantoni||PhD student||Kiehn lab|
|Michael Aagaard Andersen||Postdoc||Kiehn lab|
|Nathalie Krauth||Visiting Researcher||Kiehn Lab|
|Ole Kiehn||Professor||Kiehn lab|
|Parvaneh Sadeghi||Laboratory manager||Kiehn Lab|
|Patricia Schiødt Vase||Laboratory assistant||Kiehn Lab|
|Raghavendra Selvan||Assistant professor||Kiehn Lab|
|Rasmus von Huth Friis||Master student||Kiehn Lab|
|Roberto Leiras Gonzalez||Assistant professor||Kiehn lab|
|Roser Montañana-Rosell||PhD student||Kiehn lab|