Topological organization of the trigeminal system in the lamprey and restoration following axonal regeneration
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The nervous systems of lower vertebrates, such as the lamprey, share many of the basic features of the brain and spinal cord of higher vertebrates. However, unlike humans and other higher vertebrates, the lamprey displays robust axonal regeneration in the central nervous system following neural injuries. For example, following spinal cord transections, the descending axons of brain neurons regenerate and reconnect with spinal targets so that locomotor behavior recovers in a few weeks. The sensory and motor areas of the vertebrate nervous system often exhibit a topological or somatotopic organization, presumably to facilitate efficient transmission and processing of information. Preliminary results suggested the existence of a topological organization of the trigeminal system in the lamprey. The purpose of the current study was two-fold: (1) confirm the topological organization of the trigeminal system in normal animals; and (2) determine if this organization is restored following trigeminal nerve transection. Anatomical double labeling techniques with fluorescent tracers, Alexa 488 and TRDA, were used to confirm the existence of a topological organization in normal and trigeminal-nerve lesioned animals. First, in normal animals, the topological organization of the trigeminal nerve was confirmed. Specifically, Alexa 488 applied to the anteromedial oral hood (anterior head) labeled motoneurons in the medial part of the trigeminal motor nucleus (nVm) and sensory axons in the medial part of the trigeminal descending tracts (dV). In addition, TRDA applied to the anterolateral oral hood labeled trigeminal motoneurons in nVm and sensory axons in dV that were located laterally in these structures. Second, in trigeminal nerve-lesioned animals, the topological organization of the trigeminal system, especially in nVm, was restored. Following trigeminal nerve transection, experimental animals were separated into different recovery groups (4, 8, 12, or 16 weeks), and Alexa 488 and TRDA were applied to the same regions of the oral hood as in normal animals. The results indicate that at the longer recovery times (12 and 16 weeks), experimental animals showed a topographic organization of the trigeminal system, particularly nVm, as in normal animals. Moreover, with increasing recovery times, experimental animals recovered trigeminal-evoked escape swimming responses. Finally, electrophysiology experiments suggest that trigeminal sensory axons regenerated and synapsed with second-order sensory neurons in the brain so that trigeminal-evoked synaptic responses were restored in reticulospinal neurons. These data strongly support the existence of a topological organization of the trigeminal system in normal animals, and at least a partial restoration of this organization following trigeminal nerve transection. The restoration of the topological organization of the trigeminal system in nerve-injured lampreys suggests the possible involvement of guidance cues. For example, previous studies in fish with optic nerve lesions have shown the involvement of EphA/ephrin-A in the guidance of regenerating retinal axons and the restoration of a topological organization of the retinotectal system. For the present project, future studies might involve cell culture of trigeminal motoneurons or trigeminal sensory ganglia grown in an environment with guidance molecules (stripe assay, Dunn’s chamber), such as ephrin. Time-lapse video could be used to study the chemoaffinity between growing neurites and the molecular guidance cues. Identification of these guidance cues may provide insights into methods for improving neural regeneration in higher vertebrates, including perhaps humans.