PROTEOLYTIC ACTIVITY, SYNAPSE ELIMINATION, AND THE HEBB SYNAPSE

The Hebb synapse has been postulated to serve as a mechanism subservin g both regulation of synaptic strength in the adult nervous system (lo ng-term potentiation and depression) and developmental activity-depend ent plasticity. According to this model, pre- and postsynaptic tempora l concordance of activity results in strengthening of connections, whi le discordant activity results in synapse weakening. Evidence is prese nted that proteases and protease inhibitors may be involved in modific ation of synaptic strength. This leads to a modification of the Hebb a ssumptions, namely that postsynaptic activity results in protease elab oration with a consequent general reduction of synaptic connections to the active postsynaptic element. Further, presynaptic activity, if st rong enough, induces local release of a protease inhibitor, such as pr otease nexin I, which neutralizes proteolytic activity and produces a relative preservation of the active input. This formulation produces m any of the effects of the classical Hebbian construction, but the prot ease/inhibitor model suggests additional specific mechanistic features for activity-dependent plasticity. (C) 1994 John Wiley and Sons, Inc.