Protein Kinases and Hebbian Function

The Hebb synapse, in which the strength of synapses is affected by activity in presynaptic and postsynaptic nerve cells, is a widely used model for developmental and learning-related neuroplasticity. Presynaptic and postsynaptic firing that is correlated in time is postulated to increase synaptic strength while activity in presynaptic and postsynaptic neurons that is not correlated results in weakening. The authors describe a cell biologic, mechanistic model for activity-dependent modification of synapse strength that selectively weakens inactive inputs to activated targets. Differentially localized protein kinase A and protein kinase C molecules are activated by spike and synaptic activity. Subsequent kinase-specific phosphorylation and stabilization or destabilization of synaptic receptors are molecular and cell biologic substrates of the Hebb synapse.