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Ole Kiehn"Probing neural circuits controlling walking"

Abstract :

Locomotion is an essential motor act that for a large part is controlled by neuronal circuits in the spinal cord itself, called central pattern generators (CPGs).
The CPG activity is turned on from command systems in the brainstem. Understanding the operation of CPG circuits in mammals has been a significant challenge to neuroscientists partly due to the large number of neurons harbored in the locomotor regions and the intermingled nature of locomotor related neurons in the spinal cord and the brainstem which makes it difficult to reliably target specific neuronal subpopulations in order to elucidate the CPG circuitry and its control. However, experiments using the rodent spinal cord and combining electrophysiology and directed molecular mouse genetics to dissect the locomotor network have started to shed new light on the network structure. In this talk, I will discuss findings from my lab that have revealed the role of designated populations of neurons that serve key network functions including interneuron circuitries controlling left-right coordination and inhibitory and excitatory interneuron networks engaged in flexor-extensor alternation and rhythm-generation. I will also discuss the use of transgenic mouse models that have light-activated switches incorporated in subpopulation of neurons. These tools provide a new basis for functional probing and molecular identification of the spinal CPG and the descending command systems and their integration in the CPG. Together our experiments provide insights to the principal mode of operation of a large-scale mammalian motor circuit.

References: 1) Neuron (2011), 71(6): 1071-1084. 2) Current Opinion in Neurobiology (2010) 21(1): 100-109. 3) Nature Neuroscience (2010), 13(2): 246-245. 4) Neuron (2008), 60(1): 70-83. 5) Annual Review in Neuroscience (2006), 29: 279-306. 6) Nature (2006), 440(7081): 215-9. 7) PNAS (2005), 102(39): 14098-14103. 8) Neuron (2003), 38(6): 953-63. 9) Science (2003), 299(5614): 1889-1892.

Selected publications

Talpalar AE, Endo T, Peter P, Borgius L, Hägglund M, Dougherty KJ, Rygg J, Hnasko TS, Kiehn O (2011). Identification of minimal neuronal networks involved in flexor-extensor alternation in the mammalian spinal cord. Neuron, in press.

Restrepo CE, Margaryan G, Borgius L, Lundfald L, Sargsyan D, Kiehn O (2011). Change in the balance of excitatory and inhibitory midline fiber crossing as an explanation for the hopping phenotype in EphA4 knockout mice. European Journal of Neuroscience, in press.

Kiehn, O (2011). Development and functional organization of spinal locomotor circuits. Current Opinion of Neurobiology, 21(1):100-9
Holz A, Kollmus H, Ryge J, Niederkofler V, Dias J, Ericson J, Stoeckli ET, Kiehn O, Arnold HH. (2010). The transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance. Development, 137(24): 4249-60.

Kiehn O, Dougherty KJ, Hägglund M, Borgius L, Talpalar A, Restrepo CE. (2010) Probing spinal circuits controlling walking in mammals. Biochemical and Biophysical Research Communication, Karolinska Institutet 200 year anniversary, special issue 396(1): 11-18.

Sandrine Bertrand