Insulin receptor signaling regulates synapse numbers. (A) Electron micrographs show ultrastructural morphology of synaptic terminals that contact green fluorescent protein (GFP)-, wild-type insulin receptor (wtIR)- and dominant negative insulin receptor (dnIR)-expressing dendrites. The postsynaptic area, presynaptic area and the clustered synaptic vesicle are highlighted in light blue, green, and pink, respectively. (B) dnIR-expressing dendrites receive significantly fewer synaptic contacts compared to GFP- and wtIR-transfected dendrites. (C) Synapses that contact GFP-, wtIR- and dnIR-expressing dendrites show comparable ultrastructural synaptic maturity, determined by the area occupied by clustered synaptic vesicles relative to the area of the presynaptic terminal. (D) Schematic cartoon showing that normal tectal neurons increase total synapse number and, therefore, synaptic transmission, branch stabilization and extension in response to enhanced visual stimulation, whereas tectal neurons expressing dnIR do not increase synapse number and fail to increase synaptic function and dendritic structural plasticity.