Functional Connectivity Shapes Spine Stability in the Hippocampus

Synaptic connections between neurons determine the flow of information in the brain. Changes in synaptic weight, along with synapse formation and pruning, reshape the functional connectivity of neural circuits—key mechanisms underlying learning and memory. However, the relationship between functional strength and the structural dynamics of individual glutamatergic synapses in the living mammalian brain remains poorly understood. Specifically, how spine morphology and stability relate to functional adaptations is unclear. Here, we repeatedly recorded excitatory postsynaptic calcium transients in single postsynaptic spines of CA1 neurons in response to optogenetic stimulation of presynaptic CA3 cells in awake, head-fixed mice for over 2 weeks. We found that functional connectivity predicted both the structural stability and clustering of synaptic inputs. Spines with large responses exhibited larger volume and higher stability compared to non-responding spines. Over time, responses were highly variable at individual synapses, but stable at the dendritic level, suggesting that dendritic branches receive stable input despite large fluctuations at individual synapses.