Synaptic pruning following NMDAR-dependent LTD preferentially affects isolated synapses

Long-term depression (LTD) is an activity-dependent decrease in synaptic strength. This state initiates either a re-potentiation or a loss, aka pruning, of the synapse within hours to days following its induction. However, the precise relationship between LTD and synaptic pruning remains elusive. Using various imaging techniques and electrophysiology on neuronal cell culture, we reveal a direct relationship between LTD and synaptic pruning. All synapses that exhibit NMDAR-dependent LTD are pruned unless counteracted by input-specific activity. Additionally, we identify the post-synaptic ion channels pivotal for sensing pre-synaptic activity. Finally, we find that neighboring synapses displaying coordinated activity act as mutual safeguards against pruning. These distinctive properties mean that LTD-dependent synaptic pruning has a major impact on synapses that do not contribute to responses involved in network activity.