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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub><mml:mrow><mml:mi>R</mml:mi></mml:mrow> <mml:mrow><mml:mi>neck</mml:mi></mml:mrow> </mml:msub> </mml:math> ), and that elevated <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub><mml:mrow><mml:mi>R</mml:mi></mml:mrow> <mml:mrow><mml:mi>neck</mml:mi></mml:mrow> </mml:msub> </mml:math> accelerates spine-head voltage dynamics, shortening spinous postsynaptic potentials by up to ~ 3-fold. <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub><mml:mrow><mml:mi>R</mml:mi></mml:mrow> <mml:mrow><mml:mi>neck</mml:mi></mml:mrow> </mml:msub> </mml:math> improves the tracking of high-frequency synaptic inputs and strongly modulates <i>Ca</i> ²⁺ signaling and the potency and temporal precision of inhibitory gating in DiSs. This work identifies <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub><mml:mrow><mml:mi>R</mml:mi></mml:mrow> <mml:mrow><mml:mi>neck</mml:mi></mml:mrow> </mml:msub> </mml:math> 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.