Role of neuropsin in formation and maturation of Schaffer-collateral L1cam-immunoreactive synaptic boutons.

We report that neuropsin is involved in the synaptogenesis/maturation of orphan and small synaptic boutons in the Schaffer-collateral pathway. Most non-synaptic orphan boutons and a number of immature small synaptic boutons expressed the cell adhesion molecule L1 in presynaptic Schaffer-collateral terminals, whereas mature large boutons on mushroom spines were devoid of L1. The number of L1-immunoreactive boutons was markedly higher in neuropsin-deficient mice than in wild-type mice, whereas there were far fewer mature large boutons. L1-immunoreactive boutons were hypertrophied in the mutant mice. When a recombinant active neuropsin was microinjected into the mutant hippocampus, the number of immunoreactive synaptic boutons reverted to wild-type levels after one day. These results strongly suggest that enzymatically active neuropsin allows a maturational change of L1-immunoreactive small boutons, both orphan and synaptic, and this step may be important in synaptic plasticity based on activity-dependent structural change.