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Presynaptic inhibition is a very powerful inhibitory mechanism and, despite many detailed studies, its purpose is still only partially understood. One accepted function is that, by reducing afferent inflow to the spinal cord and brainstem, the tonic level of presynaptic inhibition prevents sensory systems from being overloaded. A corollary of this function is that much of the incoming sensory data from peripheral receptors must be redundant, and this conclusion is reinforced by observations on patients with sensory neuropathies or congenital obstetric palsy in whom normal sensation may be preserved despite loss of sensory fibers. The modulation of incoming signals by presynaptic inhibition has a further function in operating a “gate” in the dorsal horn, thereby determining whether peripheral stimuli are likely to be perceived as painful. On the motor side, the finding that even minimal voluntary movement of a single toe is associated with widespread inhibition in the lumbosacral cord points to another function for presynaptic inhibition: to prevent reflex perturbations from interfering with motor commands. This last function, together with the normal suppression of muscle and cutaneous reflex activity at rest, is consistent with Hughlings Jackson's concept of evolving neural hierarchies, with each level inhibiting the one below it.

Hypothesis: Hughlings Jackson and presynaptic inhibition: is there a big picture?