A perspective paper has been published by Marco Capogna in the last issue of the Journal of Physiology (591.19). This article comments a paper published by Lujan, Shigemoto (ex Unit members), Ito and collaborators published in the same issue of the Journal of Physiology (http://jp.physoc.org./content/591/19/4777.long). The paper by Ito & coll. is the first to dissect out the cellular process that generates molecular asymmetries in the brain. Specifically, it identifies the major histocompatibility complex class I as key molecules involved in regulation of the asymmetry of NMDA receptors at hippocampal synapses.