Neurotransmitters and the development of the embryonic chick retina

Neurotransmitters exert important influences on a variety of processes during the development of the central nervous system, including neurite outgrowth, cell migration and cell survival. In this thesis the embryonic chick retina has been used to investigate the temporal sequence in which neurotransmitter receptors develop, their influence on intracellular calcium concentration ([Ca2+]i) and their possible functions during development. Electrophysiological and Ca2+ imaging techniques show that receptors for the excitatory neurotransmitters glutamate and acetylcholine and for the inhibitory neurotransmitter GABA appear prior to synaptogenesis, suggesting possible developmental roles for these transmitters. Many of the developmental effects of glutamate and other transmitters are attributed to their ability to alter [Ca2+]i and recently it has been shown that AMPA/kainate receptors that exclude the GLUR2 subunit are Ca2+-permeable. Here the presence of Ca2+-permeable AMPA/kainate receptors in the embryonic chick retina is demonstrated both in vivo and in vitro. Retinal explants and cultures of dissociated retinal cells were treated with glutamate analogues to investigate the role of non-NMDA (AMPA/kainate) receptors during the development of the chick retina. Activation of AMPA/kainate receptors with kainate late in retinal development leads to excitotoxic cell death, however exposure to this neurotoxin early on has no affect on cell survival in both dissociated cultures and explant cultures. Cell survival in kainate is correlated with a decrease in the Ca2+-permeability of the AMPA/kainate receptor, suggesting it may play a role in cell survival during development. Activation of this receptor early in development produces a significant reduction in the number of processes extended by the cells, showing glutamate may influence neurite growth in the developing retina via activation of non-NMDA receptors