Presynaptic inhibition in the vertebrate spinal cord revisited

The present review examines the experimental evidence supporting the existe nce of central mechanisms able to modulate the synaptic effectiveness of se nsory fibers ending in the spinal cord of vertebrates. The first section co vers work on the mode of operation and the synaptic mechanisms of presynapt ic inhibition, in particular of the presynaptic control involving axo-axoni c synapses made by GABAergic interneurons with the terminal arborizations o f the afferent fibers. This includes reviewing of the ionic mechanisms invo lved in the generation of primary afferent depolarization (PAD) by GABAergi c synapses, the ultrastructural basis underlying the generation of PAD, the relationship between PAD and presynaptic inhibition, the conduction of act ion :potentials in the terminal arborizations of the afferent fibers, and t he modeling of the presynaptic inhibitory synapse. The second section of th e review deals with the functional organization of presynaptic inhibition. This includes the segmental and descending presynaptic control of the synap tic effectiveness of group-I and group-II muscle afferents, the evidence de aling with the local character of PAD as well as the differential inhibitio n of PAD in selected collaterals of individual muscle-spindle afferents by cutaneous and descending inputs. This section also examines observations on the presynaptic modulation of large cutaneous afferents, including the mod ulation of the synaptic effectiveness of thin myelinated and unmyelinated c utaneous fibers and of visceral afferents, as well as the presynaptic contr ol of the synaptic actions of interneurons and descending tract neurons. Th e third section deals with the changes in PAD occurring during sleep and fi ctive locomotion in higher vertebrates and with the changes of presynaptic inhibition in humans during the execution of a variety of voluntary movemen ts. In the final section, we examine the non-synaptic presynaptic modulatio n of transmitter release, including the possibility that the intraspinal en dings of primary afferents also release colocalized peptides in a similar w ay as in the periphery. The outcome of the studies presently reviewed is th at intraspinal terminals of sensory fibers are not hard-wired conductors of the information generated in their peripheral sensory receptors, but dynam ic systems that convey information that can be selectively addressed by cen tral mechanisms to specific neuronal targets. This central control of infor mation flow in peripheral efferents appears to play an important role in th e generation of integrated movements and processing of sensory information, including nociceptive information.