Extensive somatosensory and motor corticospinal sprouting occurs following a central dorsal column lesion in monkeys

Abstract

The corticospinal tract (CST) forms the major descending pathway mediating voluntary hand movements in primates, and originates from ∼nine cortical subdivisions in the macaque. While the terminals of spared motor CST axons are known to sprout locally within the cord in response to spinal injury, little is known about the response of the other CST subcomponents. We previously reported that following a cervical dorsal root lesion (DRL), the primary somatosensory (S1) CST terminal projection retracts to 60% of its original terminal domain, while the primary motor (M1) projection remains robust (Darian-Smith et al., J. Neurosci., 2013). In contrast, when a dorsal column lesion (DCL) is added to the DRL, the S1 CST, in addition to the M1 CST, extends its terminal projections bilaterally and caudally, well beyond normal range (Darian-Smith et al., J. Neurosci., 2014). Are these dramatic responses linked entirely to the inclusion of a CNS injury (i.e., DCL), or do the two components summate or interact? We addressed this directly, by comparing data from monkeys that received a unilateral DCL alone, with those that received either a DRL or a combined DRL/DCL. Approximately 4 months post-lesion, the S1 hand region was mapped electrophysiologically, and anterograde tracers were injected bilaterally into the region deprived of normal input, to assess spinal terminal labeling. Using multifactorial analyses, we show that following a DCL alone (i.e., cuneate fasciculus lesion), the S1 and M1 CSTs also sprout significantly and bilaterally beyond normal range, with a termination pattern suggesting some interaction between the peripheral and central lesions.

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

“…This meant that the CST was not significantly involved by this component of the lesion. The exact mediolateral extent of the DCL was also not critical, since primary afferents traversing this tract were already transected by the DRL, and the central inflammatory reaction was most important to the CST response (Darian‐Smith et al, ; Fisher et al, ).…”

“…Ten‐eleven post‐lesion weeks is considered a chronic time point in a rat, when functional recovery appears to have plateaued (Bowes & Yip, ; Keller et al, ; Kjell & Olson, ). All lesioned animals received a combined DRL/DCL lesion, since this was previously shown to induce the greatest CST sprouting in monkeys (Darian‐Smith et al, ; Fisher et al, ). Table provides individual animal details.…”

“…Electrophysiological (low threshold unitary) recordings were made to locate the region of digit/paw representation within S1. Recordings were made with a tungsten microelectrode (1.2–1.4 mΩ at 1 kHz) and peripheral stimulation performed with a camel hair brush and Von Fry filaments as described in earlier studies (Darian‐Smith et al, ; Darian‐Smith & Brown, ; Darian‐Smith, Lilak, & Alarcon, ; Fisher et al, ). The anterograde neuronal tracer biotin dextran amine (BDA, 15% aq., Sigma B9139) was injected into the area corresponding to digit 1–3 representation (D1‐3; Figure ).…”

“…We tested within‐animal effects (position along the spinal cord) using a powerful repeated measures approach that controls for individual differences in average values between rats. Regarding between‐animal comparisons (treatment groups), previous research on S1 CST sprouting in nonhuman primates revealed very large effect sizes for the same measures when comparing monkeys between lesion groups, and within lesion groups evaluated at different time points (Darian‐Smith et al, ; Fisher et al, ). Our analysis has sufficient power to detect such effects.…”

“…In mammalian evolution, the earliest cortical control of movement may well have been from the S1 CST, which suggests this pathway plays an ancient and important role (Lemon & Griffiths, ). Following cervical deafferentation injuries that involve the dorsal column, or the dorsal column and dorsal roots (DCL or DRL/DCL), part of the hand is deafferented, and both the motor and somatosensory CSTs sprout (Darian‐Smith et al, ; Fisher et al, ), over the ensuing weeks and months. The S1 CST sprouting is particularly dramatic following a DRL/DCL, and extends bilaterally well beyond the dorsal horn into the intermediate and ventral horns, and caudally as far as T5, or five segments (~2.5 cm) beyond normal range.…”