Retinal ganglion cell function: ON and OFF pathways.

The segregation of visual signals into ON and OFF pathways represents a fundamental organizing principle of retinal processing that has been conserved across vertebrates for approximately 500 million years. This division begins at the photoreceptor-bipolar cell synapse, where distinct glutamate receptor systems create opposite responses to light increments and decrements. ON bipolar cells express metabotropic glutamate receptor 6 (mGluR6), while OFF bipolar cells utilize ionotropic AMPA/kainate receptors. These parallel pathways propagate through the inner plexiform layer's stratified architecture to retinal ganglion cells, which maintain this segregation through precise dendritic targeting or combine both signals for specialized computations. Many retinal ganglion cell types arise as paramorphic pairs with similar morphologic and functional properties, differing primarily in their preference for light increments versus decrements. However, these functionally paired ON and OFF cell types exhibit consistent asymmetries in receptive field size, temporal dynamics, and contrast sensitivity that optimize visual processing for natural scenes. These pathways show differential vulnerabilities in retinal diseases and present unique challenges for therapeutic interventions including optogenetics and prosthetic devices. Understanding ON and OFF pathway organization provides crucial insights into retinal computation, visual processing efficiency, and the neural basis of contrast detection, the foundation of visual perception.