Neurotransmitters and neurodevelopment. Role of dopamine in neurite outgrowth, target selection and specific synapse formation.

Abstract

Neurotransmitters and their receptors appear early during nervous system development and are thought to play important roles in neurite outgrowth, growth cone motility, target cell selection and synaptogenesis. In vivo studies in both vertebrates and invertebrates have shown that the perturbations of embryonic transmitter expression result in abnormal morphological and synaptic development. In vitro studies have further revealed that transmitters are capable of affecting neurite outgrowth and growth cone behaviour. The precise cellular mechanisms by which neurotransmitters affect these developmental steps are, however, poorly defined. In vitro, a presynaptic neuron from the mollusc Lymnaea stagnalis releases dopamine, which induces both growth cone attraction and growth cone collapse of target and non-target cell growth cones, respectively. We propose that the ability of dopamine to differentially affect growth cone motility of two cell types results from a divergence of the dopamine receptor-activated second messenger pathways at the G-protein level. Such transmitter-receptor interactions between growth cones of specific neurons may not only induce changes in the growth cone motility, but may subsequently play an important role in target cell selection and specificity of synaptogenesis.