Segmental distribution of the motor neuron columns that supply the rat hindlimb: A muscle/motor neuron tract-tracing analysis targeting the motor end plates

• This is the first study that characterizes the motor end plate (MEP) region for the rat hindlimb.
• The MEP regions traverse the entire width of a muscle and are arranged orthogonal to the muscle fiber orientation.
• Targeting the MEP region with Fluoro-Gold leads to robust and maximal labeling of the innervating motor neurons.
• Motor neurons innervating targeted hindlimb muscles span multiple segments of the lumbosacral spinal cord.
• This study has implications for the intramuscular delivery of viral-vectors for the treatment of spinal cord injury.

Spinal cord injury (SCI) that disrupts input from higher brain centers to the lumbar region of the spinal cord results in paraplegia, one of the most debilitating conditions affecting locomotion. Non-human primates have long been considered to be the most appropriate animal to model lower limb dysfunction. More recently, however, there has been a wealth of scientific information gathered in the rat regarding the central control of locomotion. Moreover, rodent models of SCI at lumbar levels have been widely used to validate therapeutic scenarios aimed at the restoration of locomotor activities. Despite the growing use of the rat as a model of locomotor dysfunction, knowledge regarding the anatomical relationship between spinal cord motor neurons and the hindlimb muscles that they innervate is incomplete. Previous studies performed in our laboratory have shown the details of the muscle/motor neuron topographical relationship for the mouse forelimb and hindlimb as well as for the rat forelimb. The present analysis aims to characterize the segmental distribution of the motor neuron pools that innervate the muscles of the rat hindlimb, hence completing this series of studies. The location of the motor end plate (MEP) regions on the main muscles of the rat hindlimb was first revealed with acetylcholinesterase histochemistry. For each muscle under scrutiny, injections of Fluoro-Gold were then performed along the length of the MEP region. Targeting the MEPs gave rise to columns of motor neurons that span more spinal cord segments than previously reported. The importance of this study is discussed in terms of its application to gene therapy for SCI.

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