Development of cholinergic neurons of the rat retina

Biochemical and electrophysiological features of cholinergic neurons from the developing rat retina were analyzed in an attempt to identify important periods in the maturation of these neurons. Acetylcholine synthesis was assayed in intact, isolated retinas; choline acetyltransferase activity was measured in homogenates. Spontaneous and evoked acetylcholine release and certain aspects of synapse formation were examined in a retina-muscle cell culture system. In this system, retinal cells from rats of different ages were dissociated with trypsin and added to previously cultured rat striated muscle cells which served as postsynaptic targets for cholinergic neurons. The results indicate that two developmental periods can be described. The first stage occurs during the final week of gestation well before morphological signs of synapses appear. During this early period, cholinergic neurons acquire the ability to synthesize and release acetylcholine and to form functional synapses. These developing neurons progressively lose their ability to form and to maintain synapses with an inappropriate target. A second stage of maturation begins at the end of the first postnatal week. In this phase, dramatic increases in acetylcholine synthesis, choline acetyltransferase activity, and high-affinity choline uptake are coupled temporally with the morphological differentiation of synapses.