Figure 1. A Guide to Input and Output Specificity.

(A) In its simplest form, input specificity occurs when one dendrite is innervated by two types of axons and makes different types of synapses with each axon type. These differences can be based on structural, functional, or molecular properties. (B) CA3 pyramidal neurons exemplify input specificity as they have numerous axonal inputs resulting in different types of synapses including inhibitory inputs from GABA interneurons (blue) and excitatory inputs from three different sources, the entorhinal cortex (EC, green), other CA3 neurons (purple), and the dentate gyrus (DG, magenta). Specialized presynanptic mossy fiber filopodia ‘F’ are shown. (C) In its simplest form, output specificity occurs when one axon innervates two types of dendrites and makes different types of synapses with each dendrite type. As for input specificity, these differences can be based on structural, functional, or molecular properties. (D) VGluT3-expressing amacrine cells exemplify output specificity. One amacrine cell makes glutamatergic synapses (purple) when connecting to retinal ganglion cells (RGCs) that are activated (Act) by contrast and motion and glycinergic synapses (blue) when connecting to RGCs that are suppressed (Supp) by contrast and motion.