Reinnervation of the pretectum in adult rats by regenerated retinal ganglion cell axons: anatomical and functional studies.
We have investigated the specificity of reinnervation and terminal arborization of injured retinal ganglion cell (RGC) axons in the brainstem with the object of studying in a simple situation the degree to which regenerating axons are able to replicate the characteristic patterns of terminal arborization and restore normal function. We have focussed here on the pathway that is responsible for the pupillary light reflex, which is mediated through the olivary pretectal nucleus (OPN). In adult rats, the left optic nerve was transected and a segment of peripheral nerve (PN) graft was used to bridge between the retina and different regions of the ipsilateral brainstem, including the superior colliculus. After 4-13 months, regenerated RGC axons were examined in coronal sections stained for cholera toxin B subunit. RGC axons were found extending into the ipsilateral brainstem for distances of up to 6 mm. Within the pretectum, axons innervated the OPN and the nucleus of the optic tract preferentially, and formed distinctive terminal arbors within each. Within the SC axons extended laterally into the visual layers and formed a different type of arborization. On testing the pupillary light reflex, it was found in best cases to show response amplitudes which were comparable to those recorded from control intact animals. However, unlike normals, the response amplitude tended to diminish with repeated stimulation and also appeared to deteriorate with age, although responses could still be detected in some cases as long as 15 months after grafting. These results indicate that regenerating axons can selectively reinnervate denervated nuclei, where they form typical terminal arborizations, and provide the substrates for restoring functional circuitry.
Vidal-Sanz
Manuel
M
Laboratorio de Oftalmología Experimental, Universidad de Murcia, 30100 Murcia, Spain. ofmmv01@fcu.um.es
Avilés-Trigueros
Marcelino
M
Whiteley
Simon J O
SJ
Sauvé
Yves
Y
Lund
Raymond D
RD
D000818:Animals; D001369:Axons / Q000502:physiology*; D001933:Brain Stem / Q000502:physiology; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D010525:Peripheral Nerves / Q000637:transplantation*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012025:Reflex, Pupillary; D012165:Retinal Ganglion Cells / Q000502:physiology* / Q000637:transplantation*