Spine-neck electrical bottlenecks tune temporal precision and inhibitory gating in cortical pyramidal neurons: A...

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 ( $R_{\mathrm{neck}}$ ), and that elevated $R_{\mathrm{neck}}$ accelerates spine-head voltage dynamics, shortening spinous postsynaptic potentials by up to ~ 3-fold. $R_{\mathrm{neck}}$ 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 $R_{\mathrm{neck}}$ 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.