Modulation of input to the spinal cord; contribution of GABA released by interneurons and glial cells by polarization at the entry of sensory information

Modulation of input from primary afferent fibres has long been examined at the level of the first relay neurons of these fibres. However, recent studies reveal that input to the spinal cord may also be modulated before action potentials in intraspinal collaterals of afferent fibres reach their target neurons, even at the level of the very entry of afferent fibres to the spinal grey matter. Such modulation greatly depends on the actions of GABA via extrasynaptic membrane receptors. In the reported study we hypothesized that the increase in excitability of afferent fibres following epidural polarization close to the site where collaterals of afferent fibres leave the dorsal columns is due to the release of GABA from two sources: not only terminals of GABAergic interneurons but also glial cells. We present evidence, primo, that GABA from both these sources contributes to a long-lasting increase in the excitability and a shortening of the refractory period of epidurally stimulated afferents fibres and, secondo, that effects of epidural polarization on GABA-containing terminals of GABAergic interneurons and on glial cells are more critical for these changes than direct effects on the stimulated fibres. The experiments were carried out in deeply anaesthetized rats in which changes in compound action potentials evoked in hindlimb peripheral nerves by dorsal column stimulation were used as a measure of the excitability of afferent fibres. The study throws new light on the modulation of input to spinal networks but also on mechanisms underlying the restoration of spinal functions.