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bioRxiv · 10.64898/2026.02.16.706119

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

Ofer, N.·Shapira, S.·Segev, I.
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Abstract

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 (Rneck), and that elevated Rneck accelerates spine-head voltage dynamics, shortening spinous postsynaptic potentials by up to [~]3-fold. Rneck improves the tracking of high-frequency synaptic inputs and strongly modulates Ca2+ signaling and the potency and temporal precision of inhibitory gating in DiSs. This work identifies Rneck 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.

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Ofer, N., Shapira, S., Segev, I.. 2026-02-17. Spine-neck electrical bottlenecks tune temporal precision and inhibitory gating in cortical pyramidal neurons: A connectomics-based biophysical study. https://doi.org/10.64898/2026.02.16.706119

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