Paired Associative Stimulation Induces Change in Presynaptic Inhibition of Ia Terminals in Wrist Flexors in Humans

Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex. Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability. In a first series of experiments ( experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression. To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1and D2 inhibitions methods; experiment 2) and postactivation depression ( experiment 3) were determined before and after PAS. Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex. Postactivation depression was unaffected by PAS. It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals.

Early Postnatal Development of Reciprocal Ia Inhibition in the Murine Spinal Cord

The pathway mediating reciprocal inhibition from muscle spindle afferents (Ia axons) to motoneurons (MNs) supplying antagonist muscles has been well studied in adult cats, but little is known about how this disynaptic pathway develops. As a basis for studying its development, we characterized this pathway in mice during the first postnatal week, focusing on the projection of quadriceps (Q) Ia axons to posterior biceps-semitendinosis (PBSt) MNs via Ia inhibitory interneurons. Synaptic potentials in PBSt MNs evoked by Q nerve stimulation are mediated disynaptically and are blocked by strychnine, implying that glycine is the major inhibitory transmitter as in adult cats. The specificity of neuronal connections in this reflex pathway is already high at birth; Q afferents evoke inhibitory synaptic potentials in PBSt MNs, but afferents supplying the adductor muscle do not. Similar to this disynaptic pathway in cats, Renshaw cells inhibit the interposed Ia interneurons, as they reduce the disynaptic input from Q axons but do not inhibit PBSt MNs directly. Reciprocal inhibition functionally inhibits the monosynaptic excitatory reflex in PBSt MNs by P3, but this functional inhibition is weak at P1. Finally, deletion of the transcription factor Pax6, which is required for the development of V1-derived Renshaw cells, does not block development of this pathway. This suggests either that Pax6 is not required for the phenotypic development of all V1-derived spinal interneurons or that these inhibitory interneurons are not derived from V1 precursors.