An investigation into the development of calcium-dependent neurotransmitter release from isolated growth cones.

Abstract

The neuronal growth cone is a motile, expanded region at the tip of the growing axon or dendrite that is responsible for guiding neurites to their correct targets (Ramon y Cajal, 1890). This structure has received great attention in studies attempting to understand the mechanisms by which growing neuronal processes locate and recognize the appropriate sites with which they are to form synapses (Lockerbie, 1987). Once the correct target has been reached, the growth cone plays a central role in synaptogenesis, transforming into either the preor post-synaptic element (Rees, 1978). In this respect, neuronal growth cones are important structures in which to study the development of the mechanisms involved in neurotransmission. It is now clear that in culture, neurotransmitters are present in growing neurites and that the growth cones of these neurites are able to release their neurotransmitters both spontaneously and in response to electrical stimulation (Hume et al., 1983; Young & Poo, 1983). In this laboratory, we have shown that growth cones isolated from developing rat forebrain are able to take up exogenous y['Hlaminobutyric acid (['HIGABA) by a transport mechanism that appears to be identical to that found at mature, GABAergic synapses. Furthermore, growth cones can release this accumulated neurotransmitter in response to high K + stimulation. However, unlike the high K+ stimulated release of ['HIGABA from synaptosomes, the release from growth cones is largely independent of extracellular Ca2 +