Super-resolution microscopy with small quantum dots reveals neuronal receptor localization

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Although AMPA receptors (AMPAR) are known to play a key role in learning and memory, their exact role remains unclear. Previous studies tracking AMPAR in live neurons suggested that they are relatively free to diffuse and located in extra-synaptic pools. This led to the suggestion that during learning, AMPA receptors wait outside the synapse until space is made available within the synaptic membrane. CPLC postdoc Sang Hak Lee in the Selvin group showed, using super-resolution microscopy, that the majority of AMPAR is not free to diffuse, but rather confined to nano-domains in the synapse. This breakthrough was made possible by the development of ‘small’ quantum dots (sQDs; ~10 nm) in the CPLC (see Cai et al. Angew. Chem. Int. Ed. 2014). In contrast to the bulky labels used in the prior studies, sQDs enable labeled receptor proteins to enter the confined space of the synaptic cleft and to be tracked. This result was also verified using smaller, organic fluorescent dyes. Future work is still needed to determine the mechanism by which AMPAR enter the synapse and contribute to acquisition of memories. Refer to:Lee et al. eLife (2017).