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Biomedical subjects

C L Zucker

Publications and source records attributed to C L Zucker.

23 records · Page 2Linked to original sources

GABAA receptors in neurons of the nerve fiber layer in rabbit retina.

Two synapse-rich layers are well recognized in the mammalian retina, the inner and outer plexiform layers. However, synapses occur also in other layers, particularly in the innermost nerve fiber layer. These synapses form a tenuous layer at times referred to as the superficial plexiform layer. We have found that staining for GABAA receptors in whole-mounted rabbit retina demonstrates this layer. It is most well developed in the region of the visual streak 2-4 mm below the center of the myelinated streak and is very sparse in other parts. Most or all of the processes in the plexus originate from cells in the ganglion cell layer.

Animals↗

Localization of gephyrin and glycine receptor subunit immunoreactivity in the rabbit retina.

Being utilized by over 40% of the amacrine cells, glycine is considered to be a major inhibitory neurotransmitter in the retinas of all vertebrate species examined. Localization of gephyrin, which is a 93-kD peripheral membrane glycine receptor-associated anchoring protein, has been used in several studies to identify the sites of glycinergic interactions in the retina and other regions of the central nervous system. Recent studies have shown that gephyrin colocalizes with GABA(A) receptors which, like those for glycine, are also inhibitory amino acid receptors usually associated with a chloride channel. In the present study, we have used two antibodies which recognize either gephyrin (mAb7a), or the alpha and beta subunits of the glycine receptor (mAb4a) in order to determine to what extent gephyrin is associated with glycine receptors in the mammalian retina. Single-label studies showed extensive punctate staining throughout most of the inner plexiform layer with each antibody. Double labeling showed that nearly 90% of the glycine receptor sites were also immunoreactive for gephyrin. However, nearly 60% of the total punctae immunoreactive for gephyrin were not stained for glycine receptors. This distinction was most pronounced in the most proximal inner plexiform layer where only 24% of the gephyrin-immunoreactive sites were glycine receptor positive. This study suggests that although most glycine receptors in the rabbit retina colocalize with the anchoring protein gephyrin, a significant proportion of the gephyrin-labeled sites are not associated with glycine receptors. In light of studies showing gephyrin association with GABA(A) receptor subunits, the localization of gephyrin may be indicative of chloride-mediated inhibitory amino acid transmission in general and not solely that of glycinergic. Given several studies which show that bipolar cells express glycine receptors and respond to glycine but do not express gephyrin, the 10% of glycine receptors not colocalized with gephyrin shown in the present study may represent a subtype of glycine receptors found on bipolar cells which do not require gephyrin for the functional clustering of receptor subunits.

Animals↗

Centrifugal fibres synapse on dopaminergic interplexiform cells in the teleost retina.

In teleost fish, centrifugal fibres originating in the olfactory bulb and containing FMRFamide-like and luteinizing hormone releasing hormone (LHRH)-like peptides project to the retina and terminate along the border of the inner nuclear and inner plexiform layers. Using a novel simultaneous two-colour immunolabelling technique, we have found that these centrifugal fibres are often closely apposed to the dopaminergic interplexiform cells. Contacts between centrifugal fibres and dopaminergic interplexiform cells were observed by electron microscopy to be conventional type synaptic junctions. Since the dopaminergic interplexiform cells make synapses on horizontal and bipolar cells, providing an intraretinal centrifugal pathway for information flow from the inner to the outer plexiform layers, we conclude that every neuron in the teleost retina is potentially susceptible to central influences via these centrifugal fibres and dopaminergic interplexiform cells.

Animals↗

Function and structure in retinal transplants.

Embryonic mammalian donor retina transplanted into the subretinal space of a mature host develops into a graft with well-organized, but atypical retinal structure. We tested the effect of this organization on rabbit-to-rabbit graft functional properties, isolating the graft to avoid contamination of graft responses by host retinal activity. Transient ON or ON-OFF spike-like responses and local electroretinograms (L-ERGs) were recorded simultaneously via a single electrode on the graft surface. These response components depended on stimulus diameter, sometimes in a way indicating antagonistic center-surround receptive field organization and spatial tuning (43%). Other times, the responses were an increasing function of stimulus diameter which saturated for large spots (57%). Response amplitudes were a monotonically-increasing function of light intensity over the narrow range tested. The L-ERGs were reminiscent of the proximal negative response or M-wave seen in normal retinas, which reflect light-induced amacrine cell activity. Thus, for the first time, we have shown that these subretinal grafts possess light-transduction and complex functional properties like those in normal retinas. They also possess the cellular complement and synaptic microcircuitry needed to form these physiological properties, Therefore, these results demonstrate a functional ability and capacity in transplants that is required if nerve cell transplantation surgery is to be done with therapeutic aims.

Action Potentials↗

Ultrastructural circuitry in retinal cell transplants to rat retina.

The development of five transplants of fetal retinal tissue to adult rat eyes was examined with the electron microscope. The transplants were of 9 to 10 weeks total age after conception in four cases and 20 weeks in one case. They were at stage E15 when transplanted. Transplants developed in both the epiretinal and subretinal spaces. The transplants were heterogeneously developed with some parts showing almost normal differentiation and others little. Subretinal transplants examined in this study were more developed than epiretinal grafts. Photoreceptor cells developed both inner and outer segments. Their synaptic terminals possessed output ribbon synapses with postsynaptic processes similar to those seen in normal retinas. In regions corresponding to the inner plexiform layer, the adult complement of synapses was seen, including advanced features such as serial synapses as well as reciprocal synapses at bipolar cell dyads. Incompletely differentiated synapses of both the amacrine and bipolar cell types were often observed, especially in the rat epiretinal transplants. Ganglion cell processes could not be identified with certainty. Although transplant cells were adjacent to host photoreceptor cells and pigment epithelium, obvious specializations or interactions were not observed. The experiments suggest that embryonic rat retinal cell transplants develop most or perhaps all of the structural components and neuronal circuitry necessary to transduce light and process some visual information.

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