First, the proposed positioning of the DHPR tetrads with respect to the RyR1 found by TEM thin section and freeze-fracture studies locate these in domains 5-6-9. Second, studies using green fluorescent protein tags inserted along the RyR1 sequence have shown that the divergent region 2 of RyR1, a sequence crucial for the RyR1-DHPR coupling, was located between domains 6 and 8 of RyR1. The TEM thin-section studies also indicate that RyR1s form a twodimensional lattice. In the lattice, two SPRY2 domains from two adjacent RyR1s are facing each other. However it is unlikely that SPRY2 domains have a direct role in these interRyR1 interactions because two neighboring SPRY2 domains are located at a relatively large distance of each other, around 60 A˚. Finally, the location of the SPRY2 domain on the peripheral region of the cytoplasmic domain makes it also widely accessible to other protein binding partners in the cytoplasm. In conclusion, our methodological approach has allowed us to extract detailed and relevant information out of very limited amount of data. Our antibody labeling and 3D mapping of RyR1 provides new and deeper insight on the location of the SPRY2 domain in the RyR1 structure and in the context of the RyR1-DHPR interaction. Until the structure of big proteins such as RyR1 can be resolved by higher resolution techniques such as Xray crystallography, cryo-EM appears to be the best feasible alternative to identify regions in the 3D structure of proteins. Furthermore, many of the mechanisms inherent in memory are conserved from flies to mammals. Studies in Drosophila combine the use of powerful genetic tools together with the possibility of analyzing a large repertoire of behaviors. The genetic basis of olfactory learning and memory has been studied for more than 30 years in Drosophila, providing insights into some of the genes involved in short-term and long-term memory formation. Aversive olfactory memory studies generally rely on classical conditioning of an odor-avoidance response. In this paradigm, groups of flies are successively exposed to two distinct odors, only one of which is accompanied by electric shocks. Memory scores are determined by placing the flies in the center of a T-maze where they are simultaneously exposed to the two odors during one minute. Depending on the training protocol, different types of memory can be measured. Short-term memory and anaesthesia-resistant memory are formed after one cycle of training. STM is a labile memory phase sensitive to cold shock anaesthesia that lasts for a few hours. In contrast, ARM is a consolidated form of memory resistant to cold shock that can last for days. Long-term memory is also a form of consolidated memory, indicating that de novo protein synthesis is required. LTM is generated after spacedconditioning consisting of repeated training sessions, each separated by a rest period. LTM is generally thought to occur through changes in Regorafenib VEGFR/PDGFR inhibitor synaptic efficacy produced by a restructuring of synapses. The requirement for de novo gene expression during LTM formation has been widely observed in a number of different model systems.