Forelimb amputation-induced reorganization in the cuneate nucleus (CN) is not reflected in large-scale reorganization in rat forepaw barrel subfield cortex (FBS)

Abstract

We examined reorganization in cuneate nucleus (CN) in juvenile rat following forelimb amputation (n=34) and in intact controls (n=5) to determine whether CN forms a substrate for large-scale reorganization in forepaw barrel subfield (FBS) cortex. New input from the shoulder first appears in the FBS 4 weeks after amputation, and by 6 weeks, the new shoulder input comes to occupy most of the FBS. Electrophysiological recording was used to map CN in controls and in forelimb amputees during the first 12 weeks following deafferentation and at 26 and 30 weeks post-amputation. Mapping was confined to a location 300 μm anterior to the obex where a medial-to-lateral row of electrode penetrations traversed through a complete complement of cytochrome-oxidase stained clusters (called barrelettes) that are associated with the representation of the glabrous forepaw digits and pads and adjacent non-cluster zones that are associated with the representation of the wrist, arm, and shoulder. Following amputation, non-cluster zones became occupied with new input from the body/chest and head/neck, while the cluster zone remained largely devoid of new input except at the border. A regression analysis comparing controls and amputees over the first 12 weeks post-amputation found significant differences for the total area of new input from the body/chest and head/neck in the non-cluster zones, while no significant differences were found for any new input into the cluster zone. When the averaged areas of a body-part representation were re-examined as a percentage of the averaged zonal area, a non-significant increase in new input from the body was observed within the cluster zone during post-amputation weeks 2-3 that returned to baseline in the subsequent weeks. In contrast, significant differences in averaged area of body-part representations for body/chest and head/neck were found in non-cluster zones over the first 12 weeks post-amputation. The present findings suggest that reorganization occurs only within the non-cluster zones whereby new input from the body/chest and head/neck moves in and occupies the deafferented territory immediately after amputation. Additionally, the lack of significant differences in new shoulder input in either cluster or non-cluster zones over the first 12 weeks after amputation suggests that CN provides an unlikely substrate for large-scale reorganization in the FBS.

Forelimb amputation-induced reorganization in the ventral posterior lateral nucleus (VPL) provides a substrate for large-scale cortical reorganization in rat forepaw barrel subfield (FBS)

“…In the present study in adult rats, it is possible that primary afferents from the shoulder invaded the deafferented forepaw zone in CN but were functionally unexpressed. Similar findings of a mismatch between the appearance of sprouted hindlimb afferents into CN and their functional expression have been reported (Rhoades et al, 1993); however, even at 30 weeks after amputation, few cells in the central zone in CN responded to input from the shoulder, and those were localized to the outer region bordering the forepaw zone (Li et al, 2013). …”

“…While we and others suggest that the resulting SI reorganization that follows deafferentation depends on subcortical changes (Garraghty and Kaas, 1991; Li et al, 2013; Pearson et al, 2001; Rasmusson, 1996b; Stojic et al, 1998), this conclusion is not without exception (Darian-Smith and Gilbert, 1995). Previously we reported that following forelimb amputation, new input was first observed in FBS within 4 weeks after amputation and by 6 weeks, new shoulder responses could be recorded throughout most of the FBS (Pearson et al, 2003).…”

“…To address the possibility that subcortical circuits underlie the observed reorganization in SI, we began by studying the organization (Li et al, 2012) and reorganization (Li et al, 2013) of CN with the prediction that CN would show a parallel pattern of reorganization similar to that observed in SI. Like SI, CN contains clusters that are associated with the representation of the forepaw digits and pads, but unlike SI, significant new input from the shoulder was not observed within this forepaw region up to 30 weeks after amputation.…”

“…Our previous finding that CN did not play a role in large-scale cortical reorganization following forelimb amputation in young adult rats (Li et al, 2013) can be compared to studies in which forelimb amputation was carried out in neonatal rats (Lane et al, 1995). These investigators observed that, following neonatal amputation, new hindlimb afferents invaded the deafferented forelimb zone in CN and 40% of the recorded cells developed split receptive fields that included both the hindlimb and stump (Lane et al, 1995).…”

“…CN contains a centralized cluster of cells associated with the representation of the forepaw and an adjacent non-cluster region representing the wrist, arm, and shoulder (Crockett et al, 1993; Li et al, 2012; Maslany et al, 1990). Following forelimb amputation in young adult rats, little or no new shoulder input was found within the central forepaw region up to 30 weeks post amputation, suggesting that CN provides an unlikely substrate for large-scale reorganization in the FBS (Li et al, 2013). This finding is consistent with a number of studies that reported an insignificant role for CN in providing a substrate for cortical reorganization that follows forelimb amputation (Bowlus et al, 2003; Lane et al, 2008).…”