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 ms and its tail is 20 ms, independent of a large stimulation frequency range. It is an order of magnitude longer than anticipated and comparable with the decaying membrane potential time scale. It is followed by a sharp rise-time (relative RP) of merely ∼1 md 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.

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