Long anisotropic absolute refractory periods with rapid rise-times to reliable responsiveness

TL;DR

This study reveals that neurons have longer-than-expected anisotropic absolute refractory periods, followed by rapid responsiveness, suggesting complex interactions between stimulation routes and neuronal compartments.

Contribution

It provides new measurements of neuronal refractory periods showing they can exceed 10 milliseconds and depend on stimulation route and order, challenging prior assumptions.

Findings

Average anisotropic absolute RP exceeds 10 ms

Tail of RP extends up to 20 ms

Rapid rise-time of ~1 ms to responsiveness

Abstract

Refractoriness is a fundamental property of excitable elements, such as neurons, indicating the probability for re-excitation in a given time-lag, and is typically linked to the neuronal hyperpolarization following an evoked spike. Here we measured the refractory periods (RPs) in neuronal cultures and observed that an average anisotropic absolute RP could exceed 10 milliseconds and its tail 20 milliseconds, independent of a large stimulation frequency range. It is an order of magnitude longer than anticipated and comparable with the decaying membrane potential timescale. It is followed by a sharp rise-time (relative RP) of merely ~1 millisecond to complete responsiveness. Extracellular stimulations result in longer absolute RPs than solely intracellular ones, and a pair of extracellular stimulations from two different routes exhibits distinct absolute RPs, depending on their order. Our results indicate that a neuron is an accurate excitable element, where the diverse RPs cannot be attributed solely to the soma and imply fast mutual interactions between different stimulation routes and dendrites. Further elucidation of neuronal computational capabilities and their interplay with adaptation mechanisms is warranted.