The computational properties of an isolated neuron have been analyzed in detail by postsynaptic activation with caged compounds. However, new tools are needed to manipulate neurotransmission at individual synapses in order to understand how a neuron integrates physiological stimuli received from presynaptic neurons within a circuit. Here we describe a method to control neurotransmitter exocytosis at the presynaptic compartment by using a light-gated glutamate receptor (LiGluR). In chromaffin cells, LiGluR supports exocytosis by means of a calcium influx that is comparable to voltage-gated calcium channels. Presynaptic expression of LiGluR in hippocampal neurons enables direct and reversible control of neurotransmission with light, and allows modulating the firing rate of the postsynaptic neuron with the wavelength of illumination. This method constitutes an important step toward the determination of the complex transfer function of individual synapses.