Glutamate is the transmitter at synapses from the olfactory nerve (ON) to mitral (Mi)/tufted cells, but very little is known about the functional properties of this synapse. This report summarizes in vitro physiological and computational modeling studies investigating glutamatergic neurotransmission at ON-->Mi cell synapses. Single ON shocks in rat main olfactory bulb (MOB) slices elicit distinct early and late spiking components triggered, respectively, by (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainic acid (KA) and N-methyl-D-aspartate (NMDA) receptor activation. Modeling simulations showed that the placement of both AMPA/KA and NMDA receptors on Mi apical dendrites replicates the experimentally observed early and late Mi spiking responses to ON shocks. Brief, tetanic ON stimulation in vitro induced robust, selective long-term potentiation (LTP) of NMDA receptor-dependent spiking. Modeling experiments disclosed several potential mechanisms underlying the selective LTP of NMDA receptor-dependent spiking. These findings demonstrate that ON-->Mi cell transmission exhibits a novel form of plasticity whereby high frequency synaptic activity induces selective LTP of NMDA receptor-dependent spiking.