Fisher, K. M. | bioRxiv Science

bioRxiv2019

Somatosensory corticospinal tract axons sprout within the cervical cord following a dorsal root/dorsal column spinal injury in the rat.

The corticospinal tract (CST) is the major descending pathway controlling voluntary hand function in primates, and though less dominant, it mediates voluntary paw movements in rats. As with primates, the CST in rats originates from multiple (albeit fewer) cortical sites, and functionally different motor and somatosensory subcomponents terminate in different regions of the spinal gray matter. We recently reported in monkeys that following a combined cervical dorsal root/dorsal column lesion (DRL/DCL), both motor and S1 CSTs sprout well beyond their normal terminal range. The S1 CST sprouting response is particularly dramatic, indicating an important, if poorly understood, somatosensory role in the recovery process. As rats are used extensively to model spinal cord injury (SCI), we asked if the S1 CST response is conserved in rodents. Rats were divided into sham controls, and two groups surviving post-lesion for ~6 and 10 weeks. A DRL/DCL was made to partially deafferent one paw. Behavioral testing showed a post-lesion deficit and recovery over several weeks. Three weeks prior to ending the experiment, S1 cortex was mapped electrophysiologically, for tracer injection placement to determine S1 CST termination patterns within the cord. Synaptogenesis was also assessed for labeled S1 CST terminals within the dorsal horn. Our findings show that the affected S1 CST sprouts well beyond its normal range in response to a DRL/DCL, much as it does in macaque monkeys. This, along with evidence for increased synaptogenesis post-lesion, indicates that CST terminal sprouting following a central sensory lesion, is a robust and conserved response.

neuroscience↗

bioRxiv2019

Reorganization of the Primate Dorsal Horn in Response to a Deafferentation Lesion Affecting Hand Function

The loss of sensory input following a spinal deafferentation injury can be debilitating, and this is especially true in primates when the hand is involved. While significant recovery of function occurs, little is currently understood about the reorganization of the neuronal circuitry, particularly within the dorsal horn. This region receives primary afferent input from the periphery, and cortical input via the somatosensory subcomponent of the corticospinal tract (S1 CST), and is critically important in modulating sensory transmission, both in normal and lesioned states. To determine how dorsal horn circuitry alters to facilitate recovery post-injury, we used an established deafferentation lesion model (DRL/DCL - dorsal root/dorsal column) in male monkeys to remove sensory input from just the opposing digits (D1-D3) of one hand. This results in a deficit in fine dexterity that recovers over several months. Electrophysiological mapping, tract tracing, and immunolabeling techniques were combined to delineate specific changes to dorsal horn input circuitry. Our main findings show that (1) there is complementary sprouting of the primary afferent and S1 CST populations into an overlapping region of the reorganizing dorsal horn, (2) S1 CST and primary afferent inputs connect in different ways within this region to facilitate sensory integration (3) there is a loss of larger S1 CST terminal boutons in the affected dorsal horn, but no change in the size profile of the spared/sprouted primary afferent terminal boutons post-lesion. Understanding such changes helps to inform new and targeted therapies that best promote recovery. Significance statementSpinal injuries that remove sensation from the hand, can be debilitating, though functional recovery does occur. We examined changes to the neuronal circuitry of the dorsal horn in monkeys following a lesion that deafferented three digits of one hand. Little is understood about dorsal horn circuitry, despite the fact that this region loses most of its normal input after such an injury, and is clearly a major focus of reorganization. We found that both the spared primary afferents and somatosensory corticospinal efferents sprouted in an overlapping region of the dorsal horn after injury, and that larger (presumably faster) corticospinal terminals are lost, suggesting a significantly altered cortical modulation of primary afferents. Understanding this changing circuitry is important for designing targeted therapies.

neuroscience↗