ENDOGENOUS SERINE-PROTEASE INHIBITOR MODULATES EPILEPTIC ACTIVITY ANDHIPPOCAMPAL LONG-TERM POTENTIATION

Protease nexin-l (PN-1), a member of the serpin superfamily, controls the activity of extracellular serine proteases and is expressed in the brain. Mutant mice overexpressing PN-1 in brain under the control of the Thy-1 promoter (Thy 1/PN-I) or lacking PN-1 (PN-1-/-) were found t o develop epileptic activity in vivo and in vitro. Theta burst-induced long-term potentiation (LIP) and NMDA receptor-mediated synaptic tran smission in the CA1 field of hippocampal slices were augmented in Thy 1/PN-1 mice and reduced in PN-1-/- mice. Compensatory changes in GABA- mediated inhibition in Thy 1/PN-1 mice suggest that altered brain PN-1 levels lead to an imbalance between excitatory and inhibitory synapti c transmission.