Fig. 7.

A model of caspase-2 mediated synaptic plasticity and cognitive flexibility. Under basal condition, the majority of caspase-2L is localized in the nucleus. Upon NMDA stimulation, caspase-2L is exported from the nucleus into dendrites, where it mediates the cleavage of mTORC2 scaffold protein Rictor. Decreased mTORC2 level reduces the Akt activity but increases the GSK3β activity, therefore inducing AMPAR internalization and LTD. Caspase-2 deficiency impairs LTD and spine pruning, increases GluA1 level, causes faster decay kinetics, elevates anxiety level, and impairs cognitive flexibility