Figure 1.

Simplified schematic of cone and rod pathways through the retina. Right-hand side shows the cone pathway and left-hand side shows the main (scotopic) rod pathway that provides input to the cone pathway. Chemical synapses are shown as arrowheads, with white fill denoting glutamate (Glu) synapses and grey fill denoting glycine (Gly) synapses; sign-conserving and sign-inverting synapses are indicated as ‘+' and ‘−' respectively; gap junctions are indicated as ‘⊕'. Cone ON pathway comprises cone photoreceptor to ON cone bipolar cell (ON CB) to ON ganglion cell. Cone OFF pathway comprises cone photoreceptor to OFF cone bipolar cell (OFF CB) to OFF ganglion cell. The scotopic pathway begins as: rod photoreceptor to rod bipolar cell (RB) to AII amacrine cell. The AII amacrine provides sign-conserving input via connexin-36 gap junctions onto ON cone bipolar cell terminals, as well as sign-inverting glycinergic input onto OFF cone bipolar cell terminals, thereby providing push–pull signals to ON and OFF ganglion cells. The sign-inverting glutamate synapses (from cones to cone ON bipolar cells, and from rods to rod bipolar cells) use a metabotropic postsynaptic mechanism involving a G-protein cascade, whereas the other chemical synapses use ionotropic mechanisms. Light hyperpolarises the photoreceptors, so that the sign-inverting synapse generates a depolarising light response in the ON cone bipolar cell and rod bipolar cell. Not shown in this diagram are surround mechanisms and lateral interactions mediated by horizontal cells and other classes of amacrine cell, or rod pathways used at mesopic levels (modified from Robson and Frishman;¹² see Demb and Singer¹⁹ for recent review).