The Dendritic Branch Is the Preferred Integrative Unit for Protein Synthesis-Dependent LTP

Abstract

The late-phase of long-term potentiation (L-LTP), the cellular correlate of long-term memory, induced at some synapses facilitates L-LTP expression at other synapses receiving stimulation too weak to induce L-LTP by itself. Using glutamate uncaging and two-photon imaging, we demonstrate that the efficacy of this facilitation decreases with increasing time between stimulations, increasing distance between stimulated spines and with the spines being on different dendritic branches. Paradoxically, stimulated spines compete for L-LTP expression if stimulated too closely together in time. Furthermore, the facilitation is temporally bidirectional but asymmetric. Additionally, L-LTP formation is itself biased toward occurring on spines within a branch. These data support the Clustered Plasticity Hypothesis, which states that such spatial and temporal limits lead to stable engram formation, preferentially at synapses clustered within dendritic branches rather than dispersed throughout the dendritic arbor. Thus, dendritic branches rather than individual synapses are the primary functional units for long-term memory storage.