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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