Molecular correlates of spinal motor neuron functional specification and plasticity

by Pitchaiah Cherukuri
Doctoral thesis
Date of Examination:2012-10-18
Date of issue:2013-07-30
Advisor:Dr. Till Marquardt
Referee:Prof. Dr. Klaus-Armin Nave
Referee:Prof. Dr. Ernst A. Wimmer
Persistent Address: http://dx.doi.org/10.53846/goediss-3969

 

 

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Abstract

English

The precision with which motor neurons connect to functionally matched muscle fibers ultimately determines the accuracy of behavioural outputs. Motor neurons are functionally diverse and can be subdivided into distinct functional motor neuronal subtypes (FMNTs). Furthermore, the motor neuron-muscle fiber units display a high degree of adaptive plasticity in response to chronically altered activity patterns, thus assuring flexible adjustment of neuromuscular output to habitual changes. While early events in motor neuron development are well understood, much less is known regarding molecular markers or mechanisms underlying FMNT specification or function. Furthermore, while the molecular events underlying muscle fiber plasticity are well documented, neither the functional significance nor the underlying molecular mechanisms contributing to the plasticity of motor neurons are known. Using type-specific gene profiling, I identified novel markers and putative gene signatures of FMNTs in addition to determining gene signatures associated with adaptive motor neuron plasticity. Motor neuron type status appears to be inherently linked to their respective vulnerability (or resistance) towards neuromuscular diseases (NMDs). The ability to alter motor neuron type status, by targeting molecular pathways driving motor neuron plasticity, may eventually provide novel therapeutic intervention strategies aiming at ameliorating motor neuron loss in NMDs
Keywords: motor neurons, specification, function, plasticity
 
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