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Facilitation of sensory transmission to motoneurons during cortical or sensory evoked primary afferent depolarization (PAD) in humans.

Krista MetzIsabel Concha MatosYaqing LiBabak AfsharipourChristopher K ThompsonFrancesco NegroKatharina A QuinlanDavid J BennettMonica A Gorassini
Published in: The Journal of physiology (2023)
Sensory and corticospinal tract (CST) pathways activate spinal GABAergic interneurons that have axoaxonic connections onto proprioceptive (Ia) afferents that cause long-lasting depolarizations (termed primary afferent depolarization, PAD). In rodents sensory-evoked PAD is produced by GABA A receptors at nodes of Ranvier in Ia-afferents, rather than at presynaptic terminals, and facilitates spike propagation to motoneurons by preventing branch-point failures, rather than causing presynaptic inhibition. We examined in 40 human participants if putative activation of Ia-PAD by sensory or CST pathways can also facilitate Ia-afferent activation of motoneurons via the H-reflex. H-reflexes in several leg muscles were facilitated by prior conditioning from low-threshold proprioceptive, cutaneous or CST pathways, with a similar long-lasting time course (∼200 ms) to phasic PAD measured in rodent Ia-afferents. Long trains of cutaneous or proprioceptive afferent conditioning produced longer-lasting facilitation of the H-reflex for up to 2 minutes, consistent with tonic PAD in rodent Ia-afferents mediated by nodal α5-GABA A  receptors for similar stimulation trains. Facilitation of H-reflexes by this conditioning was likely not mediated by direct facilitation of the motoneurons because stimulation of sensory or CST pathways did not alone facilitate the tonic firing rate of motor units. Furthermore, cutaneous conditioning increased the firing probability of single motor units (motoneurons) during the H-reflex without increasing their firing rate at this time, indicating that the underlying excitatory postsynaptic potential (EPSP) was more probable, but not larger. These results are consistent with sensory and CST pathways activating nodal GABA A receptors that reduce intermittent failure of action potentials propagating into Ia-afferent branches. KEY POINTS: Controlled execution of posture and movement requires continually adjusted feedback from peripheral sensory pathways, especially those that carry proprioceptive information about body position, movement, and effort. It was previously thought that the flow of proprioceptive feedback from Ia afferents was only reduced by GABAergic neurons in the spinal cord that sent axoaxonic projections to the terminal endings of sensory axons (termed GABA axo neurons). Based on new findings in rodents, we provide complimentary evidence in humans to suggest that sensory and corticospinal pathways known to activate GABA axo neurons that project to dorsal parts of the Ia afferent also increase the flow of proprioceptive feedback to motoneurons in the spinal cord. These findings support a new role of spinal GABA axo neurons in facilitating afferent feedback to the spinal cord during voluntary or reflexive movements. Abstract figure legend Activation of gamma-aminobutyric-acid (GABA) A receptors on or near the nodes of Ranvier in Ia afferents (nodes, yellow) cause a net efflux of chloride ions to produce primary afferent depolarization (PAD, purple) (Hari et al., 27). PAD increases action potential conduction along the Ia axon (green arrows) by facilitating sodium channels at the nodes, which reduces commonly occurring failure of action potentials at myelinated axon branch points, resulting in a larger and more secure activation of spinal motoneurons by the Ia afferents. In humans we suggest that corticospinal and sensory pathways, known from animal studies to activate GABA neurons with axoaxonic connections to the Ia afferent (GABA axo ), can facilitate conduction in Ia afferents as assessed by the H-reflex, with a time course similar to phasic and tonic PAD. These results support the idea that activation of corticospinal and sensory pathways help to secure activation of spinal motoneurons by Ia afferents important for voluntary and reflex control of movement. This article is protected by copyright. All rights reserved.
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