Modulation of Sensory Input to the Spinal Cord by Peripheral Afferent Fibres via GABAergic Astrocytes

Abstract

A long-lasting GABA-dependent increase in the excitability of afferent fibres, and thus modulation of the sensory input to the spinal cord, may be evoked by epidural polarization. However, the direct effects of fibre polarization are short-lasting and the sustained increase in their excitability appears to be secondary to the release of GABA from nearby astrocytes. We have now investigated whether the modulation of spinal sensory input by stimulation of a peripheral nerve, previously attributed to synaptically evoked intraspinal field potentials, is evoked in a similar way. However, as neither its dependence on GABA nor its relays have been investigated, we addressed the question of whether the increase in the excitability of epidurally stimulated afferent fibres following a peripheral nerve stimulation does or does not depend on GABA and whether it might be mediated by astrocytes. The effects of conditioning stimulation of the tibial nerve were evaluated from changes in the excitability of both Group I and II muscle afferents, estimated from action potentials recorded in peripheral nerves and in field potentials recorded in the dorsal horn respectively in acute experiments on deeply anaesthetized rats. The excitability of the afferents was increased by stimulation of Group II and/or cutaneous but not Group I muscle afferents. The effects were significantly weakened by blocking GABA channels by gabazine and by astrocyte toxin L-alpha-aminoadipic acid (L-AAA), indicating that the excitability of both Group I and II afferent fibres may be modulated by GABAergic astrocytes, the new role played by astrocytes.