Environmental Determination of Neurotransmitter Functions in Developing Sympathetic Neurons

Abstract

One area of neuronal development which is particularly interesting is the interaction between cells and their environment as they migrate and differentiate. One of the techniques that has proven useful in studies of such interactions is cell culture, because of the opportunity to control both the fluid and cellular environments surrounding developing neurons. It is the ability to grow dissociated neurons in culture, either in the virtual absence of other cell types, or in the presence of any of a variety of known types of non-neuronal cells that enables to control the type of transmitter produced and the type of synapse formed by developing sympathetic neurons in culture. When sympathetic neurons are cocultured with appropriate non-neuronal cells, they develop striking cholinergic properties: they synthesize and store large amounts of acetylcholine (ACh) and use it at functional cholinergic synapses with a number of targets. Furthermore, this cholinergic induction caused by non-neuronal cells can be mediated by a diffusible factor. Neurons grown in culture medium that has been conditioned by incubation on cultures of appropriate non-neuronal cells (CM) also causes dramatic increases in (i) choline acetyltransferase activity (CAT) as measured in neuronal extracts, (ii) ACh synthesis and accumulation from [^3H] choline by living cells, and (iii) cholinergic synapse formation between the neurons. Thus the presence of certain non-neuronal cells, or a medium conditioned by them, has a profound effect on the type of transmitter chosen by the sympathetic neurons.