Segregated Glycine-Glutamate Co-transmission from vGluT3 Amacrine Cells to Contrast-Suppressed and Contrast-Enhanced Retinal Circuits

Since the introduction of Dale's principle of "one neuron releases one transmitter at all its synapses," a growing number of exceptions to this principle have been identified. While the concept of neurotransmitter co-release by a single neuron is now well accepted, the specific synaptic circuitry and functional advantage of co-neurotransmission remain poorly understood in general. Here we report Ca(2+)-dependent co-release of a new combination of inhibitory and excitatory neurotransmitters, namely, glycine and glutamate, by the vGluT3-expressing amacrine cell (GAC) in the mouse retina. GACs selectively make glycinergic synapses with uniformity detectors (UDs) and provide a major inhibitory drive that underlies the suppressed-by-contrast trigger feature of UDs. Meanwhile, GACs release glutamate to excite OFF alpha ganglion cells and a few other nonlinear, contrast-sensitive ganglion cells. This coordinated inhibition and excitation of two separate neuronal circuits by a single interneuron suggests a unique advantage in differential detection of visual field uniformity and contrast.