CONTROL OF DOPAMINE RELEASE IN THE RETINA - A TRANSGENIC APPROACH TO NEURAL NETWORKS

Dopaminergic, interplexiform amacrines (DA cells) were labeled in tran sgenic mice with human placental alkaline phosphatase, an enzyme that resides on the outer surface of the cell membrane. It was therefore po ssible to investigate their activity in vitro after dissociation of th e retina with whole-cell current and voltage clamp, as well as their c onnections in the intact retina with the electron microscope. DA cells generate action potentials even in the absence of synaptic inputs. Th is activity is abolished by the amacrine cell transmitters GABA and gl ycine, which induce an inward current carried by chloride ions, and is stimulated by kainate, an agonist at the receptor for the bipolar cel l transmitter glutamate, which opens nonselective cation channels. Sin ce DA cells are postsynaptic to amacrine and bipolar cells, we suggest that the spontaneous discharge of DA cells is inhibited in the dark b y GABAergic amacrines that receive their input from off-bipolars. Upon illumination, the GABA-inhibition is removed, DA cells generate actio n potentials, and their firing is modulated by the excitation received from on-bipolars.