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Neuronal circuitry and plasticity of the spinal cord using in-vivo electrophysiology in transgenic mice

Objective

The development of transgenic mice affecting development of spinal cord circuitry or mimicking hereditary neurological motor disorders has necessitated the development of in-vivo adult mouse preparations for electrophysiology to bridge molecular biology with the pathophysiology of phenotypes. The first goal is the development and refinement of a “mouse in-vivo spinal cord preparation” for intracellular recordings and analysis of spinal circuitry in “acute experiments” and a preparation for chronic recording of EMG and kinematics. These will be used to identify specific patterns of inputs to motoneurones in the mouse including the Ia monosynaptic EPSP, presynaptic inhibition, reciprocal inhibition, recurrent inhibition, propioceptive and exteroceptive polysynaptic inputs as well as the intrinsic properties of motoneurones. The data will not only characterise synaptic connectively in the mouse which can be compared to other species but will serve as control data for the rest of the project. The second goal is the use of the preparations to study transgenic mice with specific manipulations affecting the development of spinal neuronal circuitry. 2 mice mutants developed by Thomas Jessell (New York) and Silvia Arber (Basel) will be used. In the Er81 mutant mouse lack of a transcription factor causes Ia propioceptive afferents to terminate prematurely in the intermediate spinal cord. The second mutant model lacks the presynaptic GABAergic terminals on Ia afferent inputs to motoneurones. The researcher will investigate the plasticity occurring as a consequence. The third goal is to use the preparations to study transgenic mice with genetic mutations similar to those underlying neurological disorders in humans. For this the researcher will investigate plasticity in mice with a mutation affecting the glycine receptor, mimicking hyperekplexia in humans. SOD-1 mutants, models of ALS will also be used to investigate excitability changes at central part of motoneurone

Field of science

  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /medical and health sciences/basic medicine/physiology/pathophysiology
  • /natural sciences/biological sciences/molecular biology

Call for proposal

FP7-PEOPLE-IEF-2008
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

KOBENHAVNS UNIVERSITET
Address
Norregade 10
1165 Kobenhavn
Denmark
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 203 817,53
Administrative Contact
Hans R Hultborn (Prof.)