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

Abstract

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. Although 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 (dorsal root/dorsal column) in male monkeys to remove sensory input from just the opposing digits (digits 1-3) 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; and (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.

Longitudinal fMRI measures of cortical reactivation and hand use with and without training after sensory loss in primates

“…Remarkably, over weeks to months of recovery, the activation of the affected somatosensory cortex by inputs from the hand and dexterity of hand use returned. Similar results were obtained in monkeys after incomplete deafferentations of hand by sectioning some of the cervical dorsal roots unilaterally ( Darian–Smith and Ciferri, 2005 ; Fisher et al, 2020 ; see Darian–Smith and Fisher, 2019 for review). As reactivation of hand cortex returned, hand use in retrieving small pellets of food as in other tasks improved.…”

“…The advantages of using the reach-to-grasp task as a model to study training effects on impairment and subsequent recovery from DC-lesions are four-fold: (1) The reach-to-grasp task is widely used in stroke and spinal cord injury among a variety of animal models including rodents ( Ballermann et al, 2001 ; Krajacic et al, 2010 ; Starkey and Schwab, 2012 ; Wahl et al, 2014 ;) non-human primates and humans (e.g., Nudo et al, 1996a , b ; Darian-Smith and Ciferri, 2005 ; Fisher et al, 2020 ; Nishimura et al, 2007 , 2009 ; Murata et al, 2008 ; Rosenzweig et al, 2010 ; Nout et al, 2012a , b ; Friedli et al, 2015 ; Zaaimi et al, 2012 ). By using four distinct, complementary, and sophisticated reach and grasp tasks for macaque monkeys, Schmidlin et al (2011) showed how the behavioral data can be exploited to investigate the impact of a spinal cord lesion and to what extent a treatment may enhance the spontaneous functional recovery.…”

Highlights from the 30th Annual Meeting of the Society for the Neural Control of Movement

“…Using anterograde tracers, they showed that by 5-months post-lesion, spared fibers from deafferented digits sprouted new terminals in the cuneate, which then consolidated in number by 1-year post-lesion. Similar to their work in the spinal cord (12), they demonstrated specific changes to cuneate micro circuitry following injury and recovery, in the connections between S1, primary afferents, and local interneurons. This work suggests that interactions between sensory and motor circuits in the cuneate nucleus are plastic and play a role in functional recovery from injury.…”

Corticocuneate projections are altered after spinal cord dorsal column lesions in New World monkeys

“…The axonal arbors of these descending projections in the Cu may also expand to innervate more Cu neurons in response to the DCL. This speculation is based on the previous findings that the corticospinal projections from M1 and areas 3b and 1 contralateral to the lesion sprouted significantly and bilaterally beyond normal range in macaque monkeys at 4-5 months after DCLs (Darian-Smith et al, Fisher, Garner, & Darian-Smith, 2020;Fisher, Lilak, Garner, & Darian-Smith, 2018). In addition, approximately 40-60% of these corticospinal projection neurons send collateral axons to the brainstem Cu in macaque monkeys (Bentivoglio & Rustioni, 1986).…”