Regeneration of peptide‐containing retinofugal axons into the optic tectum with reappearance of a substance P‐containing lamina

Abstract

Twenty-five specimens of Rana pipiens were subjected to a unilateral crush of the optic nerve. Substance P (SP)-, leucine enkephalin (LENK)-, cholecystokinin octapeptide (CCK8)-, and bombesin (BOM)-like immunoreactivities were analyzed in the retinae, optic nerves, and optic tecta, 9 days to 9 months postoperatively, by means of immunohistochemical methods. Peptide-like immunoreactivity was observed in axons within the optic nerve stump retinal to the crush, as in previous studies (Kuljis and Karten, '83b, Kuljis et al., '84). Peptide-containing retinofugal axons began traversing the lesion site between 10 and 20 days postoperatively, in progressively increasing numbers. Ten to 20 days following crush of the optic nerve SP-, LENK-, and CCK8-containing axons could be found in the cerebral stump of the optic nerve and in the optic chiasm, advancing to the side of the brain deafferented by the crush. The number of axons displaying peptide-like immunoreactivity within the optic nerve, retinal or cerebral to the crush, and within the optic chiasm gradually decreased after 2–3 months. The optic nerve contralateral to the procedure displayed only occasional isolated peptide-containing fibers, as in normal optic nerves. The retinae ipsilateral and contralateral to the crush exhibited no change in the normal pattern of peptide-like immunoreactivity, including the absence of demonstrable peptide-like immunoreactivity in the somata of retinal ganglion cells. The optic tectum deafferented by the procedure underwent modifications in the pattern of peptide-like immunoreactivity identical to those reported following unilateral eye enucleation (Kuljis and Karten, '82a, '83a). The patterns of LENK-, CCK8-, and BOM-like immunoreactivities in the tectum were identical to those following irreversible retinal deafferentation as long as 9 months postoperatively. SP-like immunoreactivity, however, was gradually restored in layer 11 of Ramón y Cajal ('46; layer D of Potter, '69) of the superficial (retinorecipient) neuropil 4–6 months postoperatively. The persistence of lamina-specific depletion patterns of LENK-, CCK8-, and BOM-like immunoreactivities in reafferented tecta represents a puzzling observation. The latter findings contrast sharply with the recovery of SP-like immunoreactivity, which occurs long after apparently complete restitution of the retinofugal projection, as shown by anatomical (Stelzner et al., '81), physiological (Maturana et al., '59), and behavioral (Sperry, '44) methods. The implications of these findings are discussed with particular reference to (1) the possibility of lamina-specific reinnervation of the tectum by SP-containing retinofugal axons; (2) the possible roles of peptides in theadjustment or modulation of retinofugal input processing in the tectum; (3) the possibility of a differential capability for successful regeneration and/or specific reinnervation of the various populations of peptide-containing retinal ganglion cells; and (4) the possibility of selective death of some of the peptide-containing retinal ganglion cell populations as a result of inability to regenerate or abortive regeneration.