Evidence for brainstem and supra-brainstem contributions to rapid cortical plasticity in adult monkeys

Abstract

Cortical maps can undergo amazingly rapid changes after injury of the body. These changes involve functional alterations in normal substrates, but the cortical and/or subcortical location(s) of these alterations, and the relationships of alterations in different substrates, remain controversial. The present study used neurophysiological approaches in adult monkeys to evaluate how brainstem organization of tactile inputs in the cuneate nucleus (CN) changes after acute injury of hand nerves. These data were then compared with analogous data from our earlier cortical area 3b studies, which used the same approaches and acute injury, to assess relationships of cuneate and cortical changes. The results indicate that cuneate tactile responsiveness, receptive field locations, somatotopic organization, and spatial properties of representations (i.e., location, continuity, size) change during the first minutes to hours after injury. The comparisons of cuneate and area 3b organization further show that some cuneate changes are preserved in area 3b, whereas other cuneate changes are transformed before being expressed in area 3b. The findings provide evidence that rapid reorganization in area 3b, in part, reflects mechanisms that operate from a distance in the cuneate nucleus and, in part, reflects supracuneate mechanisms that modify brainstem changes.

Fig. 1.

Shifts in tactile receptive field locations and responsiveness during the first minutes after nerve section.Top, Transverse plane camera lucida drawings of reconstructed tracks in the CN (shaded) of two monkeys (A, B). Hand pictures of the glabrous (left) and dorsal (right) sides of the hand indicate abbreviations for digits (D1–D5), palmar pads (P), and the dorsal hand area opposite the palm (DH). Bottom, The indicated preinjury receptive fields (Pre) were recorded as two coupled electrodes were advanced stepwise from dorsal (i.e., sites1 + 9 in A and1 + 8 in B) to ventral (i.e., immediately below sites 8 + 16 inA and 7 + 14 inB) locations in the preinjury glabrous hand representation. Nerve section was then performed (each nerve was previously looped with suture to permit simultaneous sectioning), and postinjury responses (Post) were assessed as the electrodes were immediately retracted stepwise up the same tracks over the subsequent 34–49 min (Min). Note (1) preinjury tactile receptive fields that were restricted to glabrous skin shifted to dorsal hand skin within minutes, (2) shifts frequently involved changes from the glabrous to dorsal side of the same and/or adjacent digit(s), and (3) some sites became unresponsive to tactile stimuli (U). Scale bar, 500 μm.

Fig. 2.

Postinjury recording sites and related receptive fields for a representative CN transverse plane map. Top left, Transverse plane camera lucida drawing of the CN (shaded). Vertical lines indicate 15 electrode penetrations, small black dots indicate CN recording sites, hash marks indicate sites outside the CN, and larger black and white circlesindicate marker lesions (dorsal = up; medial =right). Scale bar, 1 mm. Bottom, Tactile receptive fields (black areas) for CN sites with corresponding number. Numbered sites for which no field is shown were not responsive to tactile stimulation. Note that neurons with tactile fields involving the hand were in central CN locations (e.g., tracks below sites 14, 26, 38, and 50), and all hand fields were on the dorsal (hairy) hand.

Fig. 3.

Consistently observed features of hand maps in the CN (A–F) and area 3b (G, H). Note that (1) normally in both the CN (E) and area 3b (G), the glabrous representation (gray) is continuous and large, whereas the dorsal representation (striped) occupies adjacent, discontinuous, small patches, and (2) after injury, the dorsal representation in the CN (striped) enlarged and became continuous across central CN locations normally representing glabrous inputs (A–D and F vsE), whereas the dorsal representation in area 3b also enlarged into area 3b locations normally representing glabrous inputs, but remained discontinuous and patchy (striped;H vs G) (see Fig. 7 for further examples). For CN maps, dorsal = up and medial =right. Scale bar, 1 mm. For area 3b maps, anterior = up and medial = right. Scale bar, 1 mm.

Fig. 4.

Cytochrome oxidase (CO) stained transverse section of the brainstem showing the CN (solid border) and the postinjury dorsal hand representation (areas indicated by * betweendotted lines). The postinjury dorsal hand representation occupies pars rotunda locations containing CO dense patches that are normally associated with glabrous hand inputs (Xu and Wall, 1999).Arrows indicate marker lesions at the bottoms of some of the penetrations made in this transverse plane. Dorsal =up; medial = right.

Fig. 5.

Normal and postinjury sizes of dorsal hand representations in the CN and area 3b. For CN measures (left), NORMAL MEAN indicates mean and 95% confidence interval sizes of normal CN dorsal hand representations [14 maps; Xu and Wall (1999)]; POSTINJURY 1–11 andMEAN indicate postinjury sizes of dorsal hand representations for 11 maps and their mean. For area 3b measures (right), NORMAL MEAN indicates mean and 95% confidence interval sizes of normal area 3b dorsal hand representations [3 maps; Wall et al. (1993)]; POSTINJURY 1–4 and MEAN indicate postinjury sizes of dorsal hand representations for four maps and their mean. See Results for details.

Fig. 6.

Analyses of CN and area 3b representations of subregions of the dorsal hand. A, Enlargement ratios (Postinjury/Normal) for representations of distal, proximal, radial, and ulnar subregions. Note that in both the CN and area 3b, representations of distal (i.e., digit) and radial subregions had larger postinjury enlargements than proximal and ulnar subregions. B, C, Examples of composite receptive field areas (hatching) that were represented in each of three CN (B) and three area 3b (C) postinjury maps. Note that (1) similar locations and extents of the dorsal hand were represented in individual maps at both levels, and (2) the ulnar edge was usually not represented (because of ulnar nerve section). See Results for further details.

Fig. 7.

Somatotopic gradients of receptive fields on the dorsal digits and proximal dorsal hand in CN (A–H) and area 3b (I–L) maps. A–F, Within postinjury CN dorsal hand representations (dark shading), recording sites with fields on the digits (○) typically occupied more dorsal locations, whereas sites with fields on the proximal hand (●) or that extended from the digits onto the proximal hand () typically occupied more ventral locations. G, H, Normal CN maps of the glabrous (light shading) and dorsal (dark shading) hand have a similar gradient. I–L, Analogous somatotopic gradients across the distal–proximal dorsal hand are seen in postinjury (I–K) and normal (L) dorsal hand representations (dark shading) in area 3b. For CN maps, dorsal =up and medial = right. Scale bar, 1 mm. For area 3b maps, anterior = up, medial =right. Scale bar, 1 mm. In all maps, equal density recording sites in white areas are not indicated.

Fig. 8.

Somatotopic gradients of receptive fields on the radial and ulnar dorsal hand in CN (A–H) and area 3b (I–L) maps. A–F, Within postinjury CN dorsal hand representations (dark shading), recording sites with fields on the radial hand (●) typically occupied more lateral to lateroventral locations, whereas sites with fields on the ulnar hand (○) or that extended from the radial to ulnar hand (◐) typically occupied more mediodorsal locations. G, H, Normal CN maps of the glabrous (light shading) and dorsal (dark shading) hand have a similar gradient. I–L, Analogous somatotopic gradients across the radial–ulnar hand are seen in postinjury (I–K) and normal (L) dorsal hand representations (dark shading) in area 3b. For CN maps, dorsal =up and medial = right. Scale bar, 1 mm. For area 3b maps, anterior = up and medial = right. Scale bar, 1 mm.

Fig. 9.

Somatotopic organization of digit representations in the CN (A–D) and area 3b (E–H). A–C,Shading and labeling of areas in three postinjury CN maps indicate postinjury representations of dorsal digits (Dor D) 1, 3, and, where seen, 5 in the first column, and of dorsal digits2 and 4 in the second column. Note (1) the partially shifted and overlapping locations of these representations from D1 lateroventrally toD5 (or 4) mediodorsally and (2) their rough in-register relation to normal glabrous digit representations (D). E–G,Shading and labeling of areas in three postinjury area 3b maps indicate postinjury representations of dorsal digits 1 and 3 in the third column and2 and 4 in the fourth column. Note that, similar to the CN, postinjury area 3b representations of dorsal digits occupied areas that were partially shifted and overlapping fromD1 laterally to D4 medially and were in rough register with normal glabrous digit representations (H). For CN maps, dorsal =up and medial = right. Scale bar, 1 mm. For area 3b maps, anterior = up and medial = right. Scale bar, 1 mm.

Fig. 10.

Tactile receptive fields on the hand, as seen in normal (A) and postinjury (B) conditions in the CN and in the postinjury condition in area 3b (C). See Results for details.

Fig. 11.

Postinjury and normal CN receptive fields on the dorsal hand were similar in size. Flower petal graph on the left shows sizes of all postinjury dorsal hand receptive fields in five monkeys (1 petal in eachflower = 1 receptive field). The bottom line indicates mean size, and the top lineindicates the upper 95% confidence interval distinguishing the main part of the sample from outlier fields. The histogram on theright indicates mean and 95% confidence interval (CI) sizes for normal dorsal hand fields from 10 monkeys.

Fig. 12.

Postinjury CN representations of tactile inputs from the forelimb–trunk–face in two maps (A, B).Top, Camera lucida tracings of two CNs. Dorsal =up; medial = right. Scale bar, 1 mm.Stippling indicates CN areas that contained recording sites with forelimb, trunk, and face receptive fields. These areas are located lateral and medial to the dorsal hand representation (white) and adjacent to areas with recording sites that were not responsive to tactile stimulation of the skin (black). Middle, Composite of the receptive field areas of all recording sites with forelimb–trunk–face fields that were located in the area lateral to the hand representation for the above CN. In each case, note that this skin included the forelimb, shoulder, neck, and face. Bottom, Composite of the receptive field areas of all recording sites with forelimb–trunk fields that were located medial to the hand representation for the above CN. In each case, note that this skin included the forelimb, trunk, and proximal hindlimb.

Fig. 13.

Histograms of the sizes of postinjury dorsal hand receptive fields in the CN (top) and area 3b (bottom). The distributions of CN and area 3b fields overlap; however, area 3b fields were smaller in terms of mean (arrows), mode (CN = 5%, area 3b = 2%), and upper 95% confidence (arrowheads) sizes. See Results for details.