The effect of firing on the excitability of a model motoneurone and its implications for cortical stimulation.

1. To help clarify the use of measurements of 'excitability', a simple model motoneurone receiving noisy tonic background excitation was tested with brief stimuli. Its response was determined from its PSTH (post-stimulus time histogram). The tonic background was varied from well below to well above the threshold for tonic firing. The conclusions should apply to many other neurones. 2. The response of the model to a stimulus depended upon a number of factors, including stimulus strength, synaptic membrane noise and especially whether or not the background drive elicited tonic firing. With the onset of firing, the shape of the stimulus-response curve changed drastically and the model then responded to the smallest stimulus without a threshold. When the drive was subthreshold, increasing the background excitation always increased the response to a given stimulus. However, what happened when the tonic drive exceeded the threshold for tonic firing depended upon the stimulus strength. With weak stimuli, the response increased with the drive to reach a plateau level where it was independent of the background firing rate; this occurred for stimuli comparable in size to the synaptic noise. With stronger stimuli, the response rose to a maximum for very low firing rates, but then decreased by up to 50 % to a plateau for high firing rates. Increasing the membrane noise reduced or abolished the maximum. 3. The model was also used to simulate a monosynaptic conditioning-testing paradigm. The effect of a given conditioning stimulus was then found to change with the onset of firing, including when the strength of the testing stimulus was adjusted to make the size of the test response the same in the presence and absence of firing. 4. The behaviour of real motoneurones can be expected to be at least as complex with the transition from silence to firing, so H reflex and other tests of 'excitability' must then be treated with caution. In particular, as has been observed experimentally, the response of a unit may decrease with increasing background excitation, as well as with inhibition. 5. Transferring the findings to corticospinal neurones makes it unlikely that the magnitude of the descending volley elicited by a given cortical stimulus ('excitability') will always increase with the initial level of cortical activity. In addition, the appreciable threshold for transcranial magnetic stimulation during voluntary contraction suggests that it first excites axons rather than the neural pacemakers.