NMDA receptors play an important functional role in the neuron excitability and plasticity. The conditions and consequences of their activation are of interest for many neuroscientists. This investigation was designed to explore an activation of the NMDA receptors of frog tectal neurons in vivo by a burst of spikes of individual retinotectal fiber. We show that: (1) the NMDA receptors of tectal neurons can be activated by an intense burst discharge of an individual ganglion cell (likely darkness detector) at physiological conditions. (2) Activation of the NMDA receptors is achieved, primarily, due to temporal summation and frequency facilitation of the fast non-NMDA synaptic potentials. However, it is very likely that spatial summation of the fast retinotectal synaptic potentials with excitatory synaptic potentials of recurrent connections contributes to elicit the NMDA response. (3) The activation of NMDA receptors causes a higher level of activity of tectal neuron network. The suprathreshold excitation of efferent tectal neurons is characteristic for this level. Therefore, the burst discharge of only single retinal ganglion cell can activate the tectobulbospinal tract and lead to the motor reaction.