Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal column lesions: A pathway that could contribute to recovery after spinal cord injury

Abstract

Dorsal column lesions at a high cervical level deprive the cuneate nucleus and much of the somatosensory system of its major cutaneous inputs. Over weeks of recovery, much of the hand representations in the contralateral cortex are reactivated. One possibility for such cortical reactivation by hand afferents is that preserved second-order spinal cord neurons reach the cuneate nucleus through pathways that circumvent the dorsal column lesions, contributing to cortical reactivation in an increasingly effective manner over time. To evaluate this possibility, we first injected anatomical tracers into the cuneate nucleus and plotted the distributions of labeled spinal cord neurons and fibers in control monkeys. Large numbers of neurons in the dorsal horn of the cervical spinal cord were labeled, especially unilaterally in lamina IV. Labeled fibers were distributed in the cuneate fasciculus and lateral funiculus. In three other squirrel monkeys, unilateral dorsal column lesions were placed at the cervical segment 4 (C4) level and tracers were injected into the ipsilateral cuneate nucleus. Two weeks later, a largely unresponsive hand representation in contralateral somatosensory cortex confirmed the effectiveness of the dorsal column lesion. However, tracer injections in the cuneate nucleus labeled only about 5% of the normal number of dorsal horn neurons, mainly in lamina IV, below the level of lesions. Our results revealed a small second-order pathway to the cuneate nucleus that survives high cervical dorsal column lesions by traveling in the lateral funiculus. This could be important for cortical reactivation by hand afferents, and recovery of hand use.

Intracortical connections are altered after long‐standing deprivation of dorsal column inputs in the hand region of area 3b in squirrel monkeys

“…We speculate that such surviving hand inputs may promote the use of the affected hand sooner after sensory loss (Martinez et al, ; Qi et al, ) and restrict the formation of new connections within the hand region of each hierarchical station to area 3b and to other somatosensory cortex, consequently restricting the scale of anatomical rewiring. As we show that some reactivation by tactile afferents from the hand occurs in area 3b even after a complete DCL, the second‐order neurons that survive DCLs are the likely sources of this limited activation by relaying tactile information to the Cu (Liao et al, ). These second‐order spinal cord inputs to the Cu may increase or at least become more effective after DCLs.…”

“…We did not observe the large‐scale expansion of connections that has been reported for area 1 hand neurons after hand amputation in macaque monkeys (Florence et al, ). Whereas hand amputations remove all peripheral inputs from the hand, DCLs allow hand inputs to ascend to the somatosensory system through the spared dorsal column fibers and the second‐order spinal cord pathway (Liao et al, ). We speculate that such surviving hand inputs may promote the use of the affected hand sooner after sensory loss (Martinez et al, ; Qi et al, ) and restrict the formation of new connections within the hand region of each hierarchical station to area 3b and to other somatosensory cortex, consequently restricting the scale of anatomical rewiring.…”

“…Monoclonal anti‐VGLUT2 (MAB5504, Millipore, Billerica, MA) is a mouse IgG1 antibody with clone 8G9.2, which was developed against the full length of recombinant protein from rat VGLUT2, and labels a single band at 56 kDa (Balaram et al, ). Immunoreactivity of anti‐VGLUT2 accurately recognizes VGLUT2 in primates (Balaram et al, ; Balaram and Kaas, ; Baldwin et al, ; Liao et al, ) and rats (Kaneko and Fujiyama, ).…”

De novo aging-related megaloneurites: alteration of NADPH diaphorase positivity in the sacral spinal cord of the aged dog

“…The retrograde transganglionic labeling of primary afferent fibers from the bladder (Wang et al, 1998), urethra (Vizzard et al, 1995) and external urethral sphincter (Nadelhaft and Vera, 1996), as well as from the penile nerve (McKenna and Nadelhaft, 1986) has indicated that DGC is a part of the reflex pathways that control the functions of the pelvic viscera (Palecek and Willis, 2003;Cruz et al, 2017). Some structure of the brain stem have a neuroanatomically reciprocal relationship with the lumbosacral spinal cord (Kuo and de Groat, 1985;Al-Chaer et al, 1996;Wang et al, 1999;Qi and Kaas, 2006;Liao et al, 2015). The DGC in the sacral segment is involved in the central processing of pelvic visceral information and is also associated with nociceptive, analgesia and autonomic function (Wang et al, 1999).…”

Relationship between brainstem neurodegeneration and clinical impairment in traumatic spinal cord injury

“…The brainstem is phylogenetically highly conserved in mammals and plays a key role in motor (Lemon, 2008) and sensory function (Benarroch, 2012, Liao et al, 2015). Important substructures of the motor system entail the rubrospinal system (i.e.…”