Proteolytic activity, synapse elimination, and the Hebb synapse.
The Hebb synapse has been postulated to serve as a mechanism subserving both regulation of synaptic strength in the adult nervous system (long-term potentiation and depression) and developmental activity-dependent plasticity. According to this model, pre- and postsynaptic temporal concordance of activity results in strengthening of connections, while discordant activity results in synapse weakening. Evidence is presented that proteases and protease inhibitors may be involved in modification of synaptic strength. This leads to a modification of the Hebb assumptions, namely that postsynaptic activity results in protease elaboration with a consequent general reduction of synaptic connections to the active postsynaptic element. Further, presynaptic activity, if strong enough, induces local release of a protease inhibitor, such as protease nexin I, which neutralizes proteolytic activity and produces a relative preservation of the active input. This formulation produces many of the effects of the classical Hebbian construction, but the protease/inhibitor model suggests additional specific mechanistic features for activity-dependent plasticity.
Liu
Y
Y
Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Fields
R D
RD
Fitzgerald
S
S
Festoff
B W
BW
Nelson
P G
PG
D016564:Amyloid beta-Protein Precursor; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000502:physiology; D002415:Cats; D010450:Endopeptidases / Q000502:physiology*; D017774:Long-Term Potentiation; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology; D009473:Neuronal Plasticity; D011323:Primates; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013569:Synapses / Q000145:classification / Q000502:physiology*; D009435:Synaptic Transmission; D013917:Thrombin / Q000502:physiology; D014795:Visual Pathways / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D010450:Endopeptidases; D013917:Thrombin