Calpain is back: a hypothesis revisited

UnrestrictedIn 1984, a hypothesis was proposed that boldly attempted to describe the cellular processes of learning and memory. This hypothesis implicated a protease, calpain, in initiating the restructuring of neuronal synapses following long term potentiation (LTP) or LTP-like stimulation. The authors hypothesized that this calpain-mediated restructuring of the synapse was the underlying mechanism of learning, memory formation and possibly memory consolidation. Since then, this hypothesis underwent constant scrutiny, falling in and out of favor until dissipating into the classical literature for several decades. Recently, several studies have revealed critical data about the calpain system; illuminating new aspects of the mechanisms of calpain activation in the central nervous system (CNS) and revitalizing the debate of the exact role of the calpain system in learning and memory. This project elucidates novel molecular machinery involved in calpain-mediated restructuring of the synapse following both growth factor stimulation and LTP-like stimulation, emanating from the receptor activation down to the subcellular molecular transformation. With the identification of this novel molecular machinery, this project hopes to also finally understand the enigma that is the biochemistry of learning and memory