How multiple-synapse boutons could preserve input specificity during an interneuronal spread of LTP.

A model is proposed whereby the spread of long-term potentiation (LTP) between potentiated and neighboring neurons is initiated by a retrograde signal that is restricted to the synaptic clefts of the potentiated neurons. Next, a change, such as enhanced release of neurotransmitter, occurs in the presynaptic boutons that are associated with potentiated synapses. This change affects all synapses that are located on the potentiated boutons, and leads to LTP at synapses on neighboring neurons that share multiple-synapse boutons with the initially potentiated neurons. In this model, restricting the retrograde signal to the potentiated synaptic clefts ensures the axonal-input specificity of LTP, and the induction of the secondary LTP requires the same cellular mechanisms as those of induction of the primary LTP.