Spine-neck electrical bottlenecks tune temporal precision and inhibitory gating in cortical pyramidal neurons: A connectomics-based biophysical study

Dendritic spines are nano-scale compartments that host the majority of excitatory synapses on cortical pyramidal neurons (PNs); hundreds of spines/PN also receive an inhibitory synapse (dually-innervated spines, DiSs). Using analytic theory and detailed biophysical models of ~2,000 densely reconstructed spines, we show that recurrent spine-neck narrowing substantially increases spine-neck resistance (R neck ), and that elevated R neck accelerates spine-head voltage dynamics, shortening spinous postsynaptic potentials by up to ~3-fold. R neck improves the tracking of high-frequency synaptic inputs and strongly modulates Ca 2+ signaling and the potency and temporal precision of inhibitory gating in DiSs. This work identifies R neck as a dynamic "knob", directly linking spine ultrastructure to information processing and plasticity in cortical PNs and circuits, yielding testable experimental predictions. Our "biophysics of connectomics" paradigm naturally raises computational-oriented questions, including how inhibitory "gates" in dendritic spines expand context-dependent computations, implement single-cell and network-level routing, and enable selective encoding of precise temporal patterns.