Glutamate, the major excitatory neurotransmitter in brain, activates diverse subtypes of receptors. The NMDA receptor type (NMDAR) play critical roles in both synaptic integration and plasticity. The subunit composition of these receptors, typically GluN2A and/or GluN2B containing, is controlled both by development and activity. This composition plays a crucial role in fine-tuning receptor function. Recent studies have made substantial progress in understanding the cellular and molecular underpinnings of the dynamic behavior of glutamate receptors such as NMDAR and their role in disease. Using high-resolution nanoparticle imaging we recently track single NMDAR at the surface of live neurons. This revealed that the surface distribution and dynamics of NMDAR is locally regulated by salient neuronal stimulation and, interestingly, such surface trafficking plays an instrumental role in synaptic adaptations. In models of neuropsychiatric disorders, characterised by a known altered glutamate transmission, we uncovered an altered surface dynamics of the glutamate receptors (e.g. NMDAR), opening new avenues of research for our comprehension of the glutamate receptor dysfunction in brain diseases and for future therapeutical strategies.