In normal lampreys some of the brainstem command neurons which initiate locomotion are reticulospinal (RS) neurons in the medial and posterior rhombencephalic reticular nuclei (MRRN and PRRN) that have descending axons in the latcral spinal tracts (64,65). These particular RS neurons are different than the large, identifiable Muller cells, which have their axons in the medial spinal tracts and do not contribute significantly to the initiation of locomotion. Following a complete spinal transection, larval lamprey recover locomotor function within 3-6 wks., and part of this recovery process is due to functional regeneration of descending axons arising from brainstem command neurons that have grown across the transection site and can activate the spinal locomotor networks below the lesion (61,63). In the present study the extent, time course, and specificity of this regeneration will be examined. Many of the experiments will use an in vitro brain/spinal cord preparation, in which the extracellular environment can be manipulated and intracellular recordings arc easily performed. The goals of the project are to examine four aspects of regeneration of R neurons that initiate locomotion in spinal-transected lamprey. (1) At least some of the growth of descending axons following a spinal transection is due to true neural regeneration of pre-existing R neurons. Cell markers, double labeling, and bromodeoxyuridine incorporation will be used to determine if development of new R neurons is also partly involved. (II) The extent of regeneration of descending R axons will be examined with both neurophysiological and anatomical methods. (III) In normal animals, R command neurons have axons in the lateral spinal tracts, and some of these axons only project to the rostral spinal cord while others project to more caudal regions. Physiological and anatomical methods will be used to determine if regenerating descending axons retain a certain degree of specificity and regrow in the same spinal tracts and to the same levels of the spinal cord as in normal animals. (IV) The biophysical properties and morphologies of R neurons will be compared in control animals (66) and animals that are recovering or have recovered from spinal transections. In addition, paired intracellular recordings will bc made from regenerated R neurons and spinal neurons to determine if normal connections have been restored. Together, these experiments will provide new information that will help us understand spinal cord regeneration and behavioral recovery following spinal injury. In the future, manipulations, such as spinal cord rotations and translocations, will be made to determine some of the intrinsic and extrinsic factors that affect the extent and specificity of regeneration.
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