Activity-dependent dendritic spine neck changes are correlated with synaptic strength

Significance Dendritic spines are the main recipients of excitatory information in the brain, and though it is accepted that they must serve an essential function in neural circuits, their precise role remains ill-defined. Here, using minimal synaptic stimulation, we show that spine neck length correlates inversely with synaptic efficacy. In addition, we discovered a previously unidentified form of spine plasticity following a spike timing-dependent plasticity protocol, characterized by rapid shortening of spine neck length and concomitant increases in synaptic strength. These results provide new insights for our understanding of synaptic plasticity, and could provide an explanation for the presence of thousands of long-necked spines in the dendrites of pyramidal neurons, whose somatic synaptic contribution would otherwise be small or negligible. Most excitatory inputs in the mammalian brain are made on dendritic spines, rather than on dendritic shafts. Spines compartmentalize calcium, and this biochemical isolation can underlie input-specific synaptic plasticity, providing a raison d’etre for spines. However, recent results indicate that the spine can experience a membrane potential different from that in the parent dendrite, as though the spine neck electrically isolated the spine. Here we use two-photon calcium imaging of mouse neocortical pyramidal neurons to analyze the correlation between the morphologies of spines activated under minimal synaptic stimulation and the excitatory postsynaptic potentials they generate. We find that excitatory postsynaptic potential amplitudes are inversely correlated with spine neck lengths. Furthermore, a spike timing-dependent plasticity protocol, in which two-photon glutamate uncaging over a spine is paired with postsynaptic spikes, produces rapid shrinkage of the spine neck and concomitant increases in the amplitude of the evoked spine potentials. Using numerical simulations, we explore the parameter regimes for the spine neck resistance and synaptic conductance changes necessary to explain our observations. Our data, directly correlating synaptic and morphological plasticity, imply that long-necked spines have small or negligible somatic voltage contributions, but that, upon synaptic stimulation paired with postsynaptic activity, they can shorten their necks and increase synaptic efficacy, thus changing the input/output gain of pyramidal neurons.