These animations show the activation and actions of neuronal calpains under physiological and pathophysiological conditions. They emphasize how physiological events involved in excitatory neurotransmission and synaptic plasticity—such as glutamate release, calcium influx, and activation of postsynaptic calpains—can become destructive under pathological conditions. These animations would be useful in a neurobiology or neuroscience course, where they could be used to illustrate proteolytic mechanisms underling activity-dependent synaptic plasticity, and how excessive activation of these signaling mechanisms can lead to excitotoxic neuronal death.