Recent observations in neonatal rabbit retina reveal highly complex maturation patterns for neurotransmitter systems such as gamma amino butyric acid (GABA). The normal maturation process appears to involve the emergence of GABA related properties (i.e., uptake) in a variety of different neurons followed by selective elimination of these properties postnatally in all but a limited population of neurons which represent mature, GABAergic amacrine cells. The transient expression of GABAergic properties by horizontal cells associated with the outer plexiform layer (OPL) and by ganglion cells associated with the inner plexiform layer (IPL) raise the possibility that GABA may have a unique developmental function, in addition to its role as an important inhibitory neurotransmitter in the adult retina. This suggestion is supported in general by reports that GABA acts as a trophic agent in other neuronal systems. More specific circumstantial evidence is provided by the observations that 1) horizontal cells are the pioneer elements of the OPL, forming laterally arranged processes along which growing elements of the OPL accrue, and 2) horizontal cells express GABAergic properties at a time coincident with initiation of synaptogenesis in the OPL. The overall goal is to examine the developmental processess which are responsible for functional GABAergic circuits in the adult. We propose to investigate the possibility that a) GABA can be used as a marker for horizontal (and perhaps ganglion) cells which may perform trophic functions in the development of retinal plexiform layers; and/or b) GABA itself may function as a trophic substance. Light and electron microscopy and autoradiography will be used to analyze the development of the OPL and its relationship to the 3H-GABA accumulating horizontal cell. Other autoradiographic and immunocytochemical markers will be developed to aid in this analysis. The horizontal cell will be lesioned chemically and GABAergic processes blocked in order to determine if the anatomical or chemical integrity of the horizontal cell is necessary for normal postnatal development of the OPL. Postnatal development of the GABAergic cells in the inner retina will also be monitored in these experiments. Finally, the ability of GABA accumulating cell populations to release both endogenous and exogenously applied GABA will be examined during development. Expectations are to produce fundamental knowledge about the GABA neurotransmitter system in the vertebrate retina and its relationship to neuronal development.
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