The all-or-nothing principle indicates that a nerve cell fires at maximum potential or not at all, based on a threshold on the stimulus.

Is this a statement which is always true, or only mostly-always true?

In electrical engineering, a discipline I have studied, we have a similar rule, a logic signal is responded to as though it is either a high or a low. However, in the middle are what are known as "metastable states," where the rules of thumb do not apply. In fact, you can even theoretically lock up a logic circuit by presenting a steady stimulus in between two states. Needless to say, designers of such circuits take great effort to ensure their logic is never exposed to such stimulus.

Do we have any evidence of neurons exhibiting behavior which defies the all-or-nothing law in some circumstances, or if not, what sorts of metastable behavior are seen when the stimulus is exceedingly close to that of the threshold?

  • $\begingroup$ If you only ask if it is always true or not, than here is the answer to your question: science.sciencemag.org/content/127/3296/468.short Unfortunately, I don't know any other example as of now. $\endgroup$
    – FloriOn
    Jan 28, 2016 at 17:38
  • $\begingroup$ That article refers to a bundle of muscle fibers, not nerve cells. Muscle bundles don't exhibit all-or-nothing, or you'd never be able to pick up eggs. It's interesting because heart muscle is similar to nerve tissue in a couple of respects but the all-or-nothing law doesn't apply here. $\endgroup$
    – Resonating
    Jan 28, 2016 at 20:26
  • $\begingroup$ @Resonating They are controlled via the same mechanism as nerve cells, namely action potential. The strength of contraction is determined by two things: the number of cells activated, and the frequency at which the action potentials are sent. Action potentials are of the same potential regardless of the contraction's strength. $\endgroup$
    – FloriOn
    Jan 29, 2016 at 14:38

1 Answer 1


I would argue the all-or-none principle is a rule of thumb. It is generally true if voltage hits a certain threshold then there will be a action potential with the same amplitude regardless the strength of the stimuli. But as you point out with the logic gate example, the threshold is notoriously hard to define mathematically. Furthermore Action Potentials don't always have the same amplitude, but as I will argue that doesn't matter all that much to the function of the neuron.

As most rules in biology we can find exceptions. I'll list some phenomena that confound the all or none principle.

  1. Accommodation is the prime example that not all action potentials have the same voltage amplitude. Accommodation is the when the amplitude of the voltage of successive action potentials drops, and may even stop firing (Depolarization Block). This is usually the result of a too strong of a stimulating current, and occurs under pathological conditions. A simulation of a Purkinje neuron with a lack of $Ca^{+2}$ channels causing accommodation. Note the shrinking amplitude.

  2. Resonating Neurons These neurons fire when a certain frequency of input is achieved and can even fire when hyperpolarizing (negative) currents are injected. The reason I bring this particular neuron type up is it shows that thresholds are not necessarily more depolarized (positive) than rest. They are complex manifolds (or shapes) relating to the gating variables of Ion channels in the membrane.

Hodgkin-Huxley Model under influence of a zap current. Note that the neuron resonates and fires at a certain input frequency. enter image description here

Another thing to note, is even though amplitudes of Action potential can change, the difference of a few millivolts in amplitude will not make a difference to the synapse and in that sense the all-or-none principle holds. Recall that voltage gated Calcium entry is required for a synapse to release it's neurotransmitter. Much like the logic gate, it will only enter at sufficiently depolarized (positive values) but the more positive the voltage, does not correspond to more Calcium entry. In other words it saturates at high voltages. In this way, to cause a stronger response at the synapse the neuron increases the firing frequency to stay "on average" depolarized longer. Thus more Calcium entry and thus more neurotransmitter release.


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