(a) μ-Calpain activation is necessary for synaptic potentiation during LTP induction and its inhibition prevents LTP (middle panel). m-Calpain activation during consolidation limits the extent of synaptic potentiation and its inhibition results in enhanced LTP (right panel). μ-Calpain activation is indicated by yellow triangles and m-calpain by blue squares. CI-III application is indicated by red arrows. Note that we also postulate that μ-calpain and m-calpain are differentially localized in synapses. (b) Signalling pathways downstream of μ- and m-calpain in LTP induction and consolidation. In LTP induction, μ-calpain activation, possibly resulting from Ca2+ influx through the NMDA receptors, results in SCOP truncation followed by ERK activation. In the consolidation period, m-calpain activation, possibly resulting from BDNF-mediated ERK activation13, stimulates mTOR-dependent protein synthesis through calpain-mediated PTEN degradation14, and in particular SCOP synthesis, which would restore normal SCOP levels, thereby preventing ERK activation.