MORPHOLOGIC AND NEUROCHEMICAL TARGET SELECTIVITY OF REGENERATING ADULT PHOTORECEPTORS IN-VITRO

Regenerating adult central nervous system (CNS) neurons must re-establ ish synaptic circuits in an environment very different from that prese nt during development. However, the complexity of CNS circuitry has ma de it extremely difficult to assess the selectivity and mechanisms of synaptic regeneration at the cellular level in vivo. The synaptic pref erences of adult photoreceptors were examined by using a defined cell culture system known to support regenerative process growth, presynapt ic varicosity formation, and establishment of functional synapses. Imm unolabeling for synaptic vesicle protein 2 and ultrastructural analysi s demonstrated that cell-cell contacts made by photoreceptors were syn aptic in nature. Target selectivity was determined by quantitative ana lysis of contacts onto normal and novel target cell types in cultures in which opportunities to contact all retinal cell types were present. Target cells were identified by morphology and immunolabeling for the amino acid neurotransmitters glutamate, aspartate, gamma-aminobutyric acid (GABA), and glycine. Regenerating photoreceptors showed a strong preference for novel multipolar cell targets (amacrine and ganglion c ells) over normal photoreceptor, horizontal, and bipolar cell targets. Additionally, photoreceptors were selective for targets containing th e transmitter GABA. These results indicate first, that the normal syna ptic partners for photoreceptors are not intrinsically the optimal tar gets for regenerative synapse formation, and second, that GABA may mod ulate synaptic targeting by adult photoreceptors. (C) 1996 Wiley-Liss. Inc.