Dopamine neurons of the retina: a simple method system for studying synaptic regulatory mechanisms

In the essay we have described what we consider to be criteria for the selection of a simple mammalian model system for studying synaptic mechanisms and have shown how the dopamine-containing amacrine neuronal system of the rat retina fit these criteria. Thus, the retina contains a defined population of neurons which secrete dopamine. The neuronal activity of the dopamine-containing cells can be reproducibly controlled by the experimenter using a physiological stimulus, light. The neurons are activated by exposure to light and are relatively quiescient in the dark. We have described how this model system has been employed to study the regulation of dopamine synthesis in response to both short term and long term changes in neuronal activity. Short term exposure to light increases dopamine turnover and activates tyrosine hydroxylase, which is characterized by a decrease in the Km of the enzyme for the pteridine cofactor. After long term exposure to light the Km for the cofactor returns to the value found for animals in the dark, while the Vmax of the enzyme increases. The change of Vmax is the consequence of an increase in the specific activity of the enzyme. Evidence has also been presented illustrating the usefulness of the dopamine neuronal system of retina for studying postsynaptic mechanisms. Retina appears to contain only D-1 receptors, which are linked to adenylate cyclase. Since dopamine release in the retina can be experimentally manipulated by light, it may be possible to study the consequence of prolonged activation of receptors by dopamine on postsynaptic biochemistry.