Cellular degeneration and synaptogenesis in the developing retina of the rat

Abstract

We have investigated the time course and magnitude of cellular degeneration in the ganglion cell layer and the presumptive amacrine and bipolar regions of the inner nuclear layer during the development of the retina in the rat. Pyknotic profiles are present in the ganglion cell layer during the first 2 postnatal weeks, reaching peak numbers during the first 4 postnatal days (corresponding to the time of greatest loss of ganglion cells and their axons: Potts et al., '82; Lam et al., '82; Perry et al., '83). Two observations suggest that the majority of pyknotic profiles present in the ganglion cell layer during the second postnatal week are not ganglion cells. First, following injection of kainic acid into one superior colliculus, degenerating ganglion cells in the contralateral retina are cleared within 24-48 hours. Therefore, since most ganglion cell and axon loss occurs within the first postnatal week, few of the pyknotic profiles present in the second week are likely to be ganglion cells. Second, the time course of cellular degeneration in the ganglion cell layer during the second postnatal week follows a very similar pattern to that seen in the presumptive amacrine sublayer of the inner nuclear layer. Such a correspondence suggests that two phases of cell death occur in the ganglion cell layer: during the first postnatal week the majority of dying cells are ganglion cells, and in the second, most cell death is due to a loss of displaced amacrine cells. In the inner nuclear layer pyknotic profiles are most numerous in the presumptive amacrine region on postnatal days 6 and 7, and in the presumptive bipolar region on day 10. Synaptogenesis in the inner plexiform layer occurs later but reflects the order of cell death. Thus, conventional (presumed amacrine) synapses were first observed on day 11 and synaptic ribbons (indicative of bipolar synapses) on day 13. These observations suggest that amacrine and bipolar cells initiate synapses only after their numbers have stabilized.

Presynaptic Initiation by Action Potentials of Retrograde Signals in Developing Neurons

“…The occurrence of retrograde (as we shall argue) changes so soon after saxitoxin injection is remarkably rapid, given that retrograde transport from the eye to the ION takes almost 3 hr in E13-E14 embryos (Clarke and Cowan, 1976), but it is compatible with the fastest effects reported in other systems after axotomy: increased pyknotic counts after 4 hr for axotomized retinal ganglion cells in neonatal rats (Horsburgh and Sefton, 1987;Harvey and Robertson, 1992) or after 8 -10 hr for axotomized motor and sensory neurons in chick embryos (Oppenheim et al, 1990). The timing of retrograde effects after target activity blockade has not been investigated previously.…”

“…Moreover, many of the target cells are believed to be "proprioretinal cells" projecting from ventral to dorsal retina (Catsicas et al, 1987), and retrogradely labeled proprioretinal cells all disappear rapidly after a kainate injection into the eye (M. Catsicas, unpublished data). The present slow retrograde reaction to kainate contrasts with the very rapid reaction (4 hr) in neonatal rats of retinal ganglion cells to intracollicular kainate injection (Horsburgh and Sefton, 1987). Because of this discrepancy and because in our experiments spilled contents of the kainate-killed retinal cells might have provided temporary trophic support to the isthmo-optic axons, our case cannot be based solely on the slow reaction of the ION to intraocular kainate.…”

Group I Metabotropic Glutamate Receptors mGluR1α and mGluR5a: Localization in Both Synaptic Layers of the Rat Retina

“…Although mGluR1␣ was expressed before mGluR5a, both receptors were first present in the IPL, where the earliest synapses form during retinal development (Horsburgh and Sefton, 1987). Only later in development both mGluRs were expressed in neuronal somata in the INL and their processes in the OPL, where synapse formation occurs later than in the IPL.…”

Localization and developmental expression of the NMDA receptor subunit NR2A in the mammalian retina

“…Previous investigations of synaptogenesis in the rat report that a few conventional synapses can be observed at P11 and P12, whereas ribbon synapses are first observed at P13 (Horsburgh and Sefton, 1987). Using criteria for classification of synapses in the adult, the conventional synapses would be considered to arise from amacrine cells and the ribbon synapses from bipolar cells (Dowling and Boycott, 1966;Dubin, 1970).…”