Glucocorticoid regulation of synaptic development.

The effect of glucocorticoid hormones on the developmental step in which a presynaptic neuron acquires the ability to transmit excitatory information across a synapse was explored using a retina muscle cell culture system. Cholinergic neurons dissociated from the perinatal rat retina form functional synapses in culture with rat striated muscle cells. Early in the functional maturation of these retina muscle synapses, there is a period in which release of acetylcholine occurs spontaneously, but cannot be evoked. This stage is followed by the emergence of neurotransmitter release that is stimulus-evoked and dependent on extracellular calcium. Here, it is reported that glucocorticoid hormones accelerate this developmental sequence. Experimental findings indicate that this hormonal effect occurs at physiological concentrations, involves glucocorticoid receptors, acts at the transcriptional level and requires protein synthesis. A hypothesis is that glucocorticoids regulate the development of mechanisms which couple neuronal depolarization with release of neurotransmitter. The acceleration of the functional maturation of cholinergic retinal neurons also can occur in utero if pregnant rats are injected with a synthetic glucocorticoid or stressed by cold exposure. Thus, alterations in the time-course of synaptic maturation are not restricted to manipulation of culture conditions. The results presented here indicate that glucocorticoid hormones can regulate the timing of the developmental step in which cholinergic neurons of the rat retina become capable of releasing acetylcholine in response to excitatory stimulation.