Early odorant experience and neural activity are essential for refining developing neural connections. Although neural activity-induced synaptic plasticity is one of the most important cellular mechanisms underlying the refinement of neural circuits, whether and how natural odorant experience induces long-term plasticity in the olfactory bulb remains unknown. In vivo perforated whole-cell recording from mitral cells (MCs) in larval zebrafish showed that odorant experience induced persistent modification of developing olfactory bulb circuits via spike timing-dependent plasticity (STDP). Repetitive odorant stimuli paired with postsynaptic spiking in a critical time window (pre-post, positive timing) resulted in persistent enhancement of glutamatergic inputs from olfactory sensory neurons, but long-term depression within the opposite time window (post-pre, negative timing). Furthermore, spike-timingdependent potentiation (tLTP) in STDP induced by repetitive odorant stimulation had similar cellular processes to those of electrical stimulation-induced tLTP. Finally, odorant input induced STDP required the activation of postsynaptic N-methyl-D-aspartate receptors (NMDARs). Thus, the NMDAR is likely to be a postsynaptic coincidence detector responsible for the sensory experience-dependent refinement of developing connections. (C) 2020 Elsevier Inc. All rights reserved.