The hypothesis of a common origin for the high-order memory centers in bilateral animals is based on the evidence that several key features, including gene expression and neuronal network patterns, are shared across several phyla. Central to this hypothesis is the assumption that the arthropods' higher order neuropils of the forebrain [the mushroom bodies (MBs) of insects and the hemiellipsoid bodies (HBs) of crustaceans] are homologous structures. However, even though involvement in memory processes has been repeatedly demonstrated for the MBs, direct proof of such a role in HBs is lacking. Here, through neuroanatomical and immunohistochemical analysis, we identified, in the crab Neohelice granulata, HBs that resemble the calyxless MBs found in several insects. Using in vivo calcium imaging, we revealed training-dependent changes in neuronal responses of vertical and medial lobes of the HBs. These changes were stimulus-specific, and, like in the hippocampus and MBs, the changes reflected the context attribute of the memory trace, which has been envisioned as an essential feature for the HBs. The present study constitutes functional evidence in favor of a role for the HBs in memory processes, and provides key physiological evidence supporting a common origin of the arthropods' high-order memory centers.L earning skills vary across species depending upon specific adaptations to environmental features (1). However, beyond such adaptations, different species share many of the basic mechanisms involved in learning and memory. Both the molecular machinery involved in neural plasticity and the dynamics of the memory processes are conserved throughout evolution (2-5). This characteristic is critical to the hypothesis of a common origin of the high-order memory centers in bilateral animals (6, 7), centers that play a fundamental role in learning and memory by orchestrating high-order sensory processing within contextual frameworks (8, 9). The idea that these centers evolved from the same structure in a common ancestor has been reborn after the remarkable study of Tomer et al. (7) indicating deep homology of mushroom bodies (MBs) and the vertebrate pallium that dates back the origin of higher brain centers to the protostome-deuterostome ancestor times. The vertebrate pallium and the annelid MBs have a conserved overall molecular brain topology and neuron types (7). Furthermore, MBs and the hippocampus' dentate gyrus share the ability to generate new neurons during adult life (6,10,11). In this context, a recent study by Wolff and Strausfeld (6) has proposed that the similarities in both neuronal architectures and protein expression patterns between the mammalian hippocampus, the MBs, and the hemiellipsoid bodies (HBs) of crustaceans are important indicators of genealogical correspondence.MBs are complex paired structures of the forebrain of invertebrate species and have been vastly studied in insects (12). Since their description in the mid-1850s, the MBs have been considered higher order brain centers involved in memory...