Although the synaptic and functional organization of the vertebrate retina is fairly well understood, little is known about the cellular mechanisms regulating neuromal differentiation, maturation and synaptogenesis. We have recently used neurotransmitter-specific properties such as uptake, synthesis and release as physiological and anatomical probes to follow the development of identified neurons and synapses in the Xenopus and rabbit retinas. We found that for each of the retinal transmitters examined (GABA, glycine and dopamine), the emergence and maturation of transmitter-specific properties follow a characteristic temporal pattern. Furthermore, the commitments of neurons to become GABAergic, glycinergic and dopaminergic occur many stages prior to the expression of other currently available morphological and physiological markers. Thus, transmitter-specific properties may be powerful tools to follow morphologically and chemically the early events of differentiation as well as maturation of identified neurons. Accordingly, over the next five years, we plan to continue and extend these studies. There are 6 main objectives: (1) The developmental patterns for cholinergic and certain peptidergic neurons in the rabbit retina will be characterized and compared with those of GABAergic, glycinergic and dopaminergic systems. (2) The differentiation and maturation of GABAergic, glycinergic and dopaminergic synapses in the rabbit retina will be followed by a combination of high-affinity uptake of 3H-transmitters and electronic microscope autoradiography. (3) The developmental patterns of the post-synaptic receptors for some of these transmitters and peptides will be examined by binding and functional assays. (4) Our results on normal retinal development will be used as the basis to examine the effects of specific perturbations, such as selection lesion of an identified cell type addition of certain transmitters and drugs to the retinas, as well as light- and dark-rearings, on the development of various transmitter-specific neurons. (5) Embryonic Xenopus retinas will be dissociated into single cells and the development of transmitter-specific properties in these cells will be followed in tissue culture. (6) Retinal regeneration in the adult newt will also be studied using neurotransmitters as probes.

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National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Baylor College of Medicine
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Peng, Y W; Lam, D M (1991) Organization and development of horizontal cells in the goldfish retina, I: The use of monoclonal antibody AT101. Vis Neurosci 6:357-70
Li, H B; Lam, D M (1990) Synaptic organization of neurotensin immunoreactive amacrine cells in the chicken retina. J Comp Neurol 294:252-61
Li, H B; Lam, D M (1990) Localization of neuropeptide-immunoreactive neurons in the human retina. Brain Res 522:30-6
Li, T; Wu, S M; Lam, D M et al. (1990) Localization of classical neurotransmitters in interneurons of the larval tiger salamander retina. Invest Ophthalmol Vis Sci 31:262-71
Quarless, S A; Lam, D M (1989) Expression of high molecular weight astroglial extracellular proteins is altered by growth environment. Glia 2:403-11
Pachter, J A; Marshak, D W; Lam, D M et al. (1989) A peptide histidine isoleucine/peptide histidine methionine-like peptide in the rabbit retina: colocalization with vasoactive intestinal peptide, synaptic relationships and activation of adenylate cyclase activity. Neuroscience 31:507-19
Watt, C B; Li, T; Lam, D M et al. (1988) Quantitative studies of enkephalin's coexistence with gamma-aminobutyric acid, glycine and neurotensin in amacrine cells of the chicken retina. Brain Res 444:366-70
Yang, S Z; Watt, C B; Lam, D M et al. (1988) Localization of neurotensin-like immunoreactive amacrine cells in the larval tiger salamander retina. Exp Brain Res 70:33-42
Watt, C B; Yang, S Z; Lam, D M et al. (1988) Localization of tyrosine-hydroxylase-like-immunoreactive amacrine cells in the larval tiger salamander retina. J Comp Neurol 272:114-26
Oyster, C W; Takahashi, E S; Fry, K R et al. (1987) Ganglion cell density in albino and pigmented rabbit retinas labeled with a ganglion cell-specific monoclonal antibody. Brain Res 425:25-33

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