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Cerebral PlasticityNew Perspectives$

Leo M. Chalupa, Nicoletta Berardi, Matteo Caleo, Lucia Galli-Resta, and Tommaso Pizzorusso

Print publication date: 2011

Print ISBN-13: 9780262015233

Published to MIT Press Scholarship Online: August 2013

DOI: 10.7551/mitpress/9780262015233.001.0001

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Subcortical Contributions to Cortical Reorganization after Massive Somatosensory Deafferentation

Subcortical Contributions to Cortical Reorganization after Massive Somatosensory Deafferentation

(p.303) 24 Subcortical Contributions to Cortical Reorganization after Massive Somatosensory Deafferentation
Cerebral Plasticity

Graziano Alessandro

Jones Edward G.

The MIT Press

Abstract and Keywords

This chapter describes the sprouting hypothesis, underlining its inadequacy in the face of experimental and clinical evidence. It presents the atrophy view and illustrates its potential for explaining both short- and long-term cortical plasticity after central and peripheral denervation. It demonstrates that transneuronal atrophy and withdrawal of the axons of deafferented neurons from centers higher in the somatosensory pathway is likely to contribute to cortical reorganization. This chapter suggests that a neurodegenerative process leading to anatomical and functional reorganization of thalamus and cortex at all stages of peripheral and central deafferentations likely to be a powerful inducement of representational plasticity.

Keywords:   cortical plasticity, peripheral denervation, transneuronal atrophy, deafferented neurons, somatosensory pathway, cortical reorganization, thalamus, cortex, deafferentations

The primary somatosensory cortex (SI) of primates contains a finely detailed, topographically organized representation of cutaneous and deep receptors on the contralateral side of the body (Penfield and Rasmussen, 1950). In the adult brain, somatosensory maps are relatively stable (Dreyer et al., 1975), but events that disrupt the normal sensory input from the periphery cause changes in their topographic organization. For example, silencing afferent input from one or two digits, by amputation, peripheral nerve transection, or spinal cord lesion, will at first cause silencing of the cortical representation of those digits, followed by expansion of the cortical representations of adjacent digits with intact input into the silenced region of cortex (Kaas et al., 1983; Merzenich et al., 1983; Merzenich et al., 1984). The inverse holds for increased input activity, by which the overuse of a digit causes its cortical representation to expand at the expense of adjacent representations (Allard et al., 1991; Jenkins et al., 1990; Recanzone et al., 1990; Recanzone et al., 1992a; Recanzone et al., 1992b; Recanzone et al., 1992c). These shifts can be very large; after amputation of the upper limb, or its complete sensory deafferentation by dorsal root transections or lesions of the dorsal columns of the spinal cord, the face representation in SI, which lies lateral to the upper limb representation, expands medially up to 14 mm in macaque monkeys (Pons et al., 1991) or 20 mm in humans (Elbert et al., 1994), and in the long term, the face representation may completely replace the silenced representation of the deafferented arm.

Plasticity of somatosensory cortical and subcortical neurons after limited denervation has been extensively studied, and some of its mechanisms are relatively well understood. Very rapid changes depend on uncovering of silent synapses and release of GABA-mediated inhibition, followed in the short tem by modulation of synaptic efficacy (Buonomano and Merzenich, 1998; Calford, 2002; Cowan et al., 2003; Wall, 1977). These synaptic mechanisms will not be discussed here. By contrast, mechanisms underlying the extensive plasticity that follows long-term massive deafferentation (Jones and Pons, 1998; Pons et al., 1991) are less well understood. This is very unfortunate, because cortical reorganization may form the physiological substrate of phantom sensations in amputees and in patients with spinal cord injuries. Deafferentation pain, for example, is invariably associated with significant reorganization of cortical somatosensory maps (Flor et al., 1995). There are three lines of evidence that support this association. First, (p.304) procedures that temporarily control pain cause immediate and reversible normalization of the reorganized cortical maps (Birbaumer et al., 1997; Huse et al., 2001). Second, pathological conditions causing chronic pain of peripheral origin—for example, chronic back pain or complex regional pain syndrome—are accompanied by cortical map reorganization (Flor et al., 1997; Pleger et al., 2004). Finally, in conditions of intensive use of a body part, such as a hand in professional musicians, dystonia is a common occurrence, a condition characterized by intense pain in the affected hand and large expansion of its cortical sensorimotor representation (Candia et al., 2003). It is clear, therefore, that understanding the mechanisms leading to long-term cortical reorganization represents a fundamental step toward unveiling the central mechanisms of pain and controlling its most debilitating manifestations, such as chronic and central pain.

Two major hypotheses have been advanced in order to explain the mechanisms underlying massive long-term expansions of cortical maps: either sprouting of axons of nondeafferented central neurons with the formation of synapses on deafferented neurons (Kaas et al., 2008) or withdrawal of overlapping inputs from atrophying deafferented neurons to reveal hitherto silent inputs from body parts with intact innervation (Jones, 2000). In this chapter, we will first discuss the sprouting hypothesis, underlining its inadequacy in the face of experimental and clinical evidence. Secondly, we will present the atrophy view and show its potential for explaining both short- and long-term cortical plasticity after central and peripheral denervation.

The Case for New Axon Growth

A number of studies have shown that peripheral deafferentation can induce new axon growth from spared portions of the periphery to innervate deafferented regions in the CNS. For example, Jain et al. (2000) reported that, after cutting the cuneate fasciculus at cervical levels in New World monkeys, and later injecting an anterograde axonal tracer in the skin of the chin and lower face, terminal labeling could be found in the ipsilateral cuneate nucleus on the side of the spinal lesion. By using a similar technique, the same group also reported new growth of cortical axons from neurons in area 3b of SI, innervating larger-than-normal portions of area 1 in monkeys with disrupted somatosensory input (Florence et al., 1998). In both studies, the tracing experiments were accompanied by extensive mapping of the cortical body representation, and the authors proposed that new axonal growth at cortical or subcortical levels is necessary and sufficient for large-scale cortical map plasticity after massive deafferentation. For a number of reasons, such evidence, and the conclusions derived from it, should be interpreted carefully, especially in regard to a causal role of sprouting in cortical reorganization.

First, more parsimonious explanations can account for the presence of anterogradely labeled axons from the skin of the chin in the cuneate nucleus. Jain et al.’s (2000) interpretation that their results indicated sprouting of trigeminal axons into the cuneate nucleus is open to question. In primates, the transverse cutaneous nerve of the neck, whose axons enter the spinal cord at C2−C3 level and terminate in the cuneate nucleus, extends its innervation field from the neck as far as the chin, overlapping the field innervated by the mandibular branch of the trigeminal (p.305) nerve (Carpenter and Sutin, 1983; Sherrington, 1939). It is not surprising, therefore, to find anterogradely labeled axons in the cuneate nucleus after tracer injections in the chin area. To draw conclusions on the causal role of brainstem sprouting in cortical reorganization (Jain et al., 2000), it would be necessary to closely control the amount of tracer and the extent of the area injected, in conjunction with a detailed evaluation of cortical map reorganization, and this has yet to be done. The significance of this observation becomes all the more evident by considering that the region of periphery where trigeminal and cuneate projecting nerves overlap corresponds to the same portions of cortical and thalamic face representations which expand into those of a deafferented hand (Jones and Pons, 1998; Pons et al., 1991); these cortical and thalamic representations are characterized by dense reciprocal connectivity (Manger et al., 1997). The evidence for sprouting of cortical axons after disruption of somatosensory input (Florence et al., 1998) suffers from a similar shortcoming, in that it may depend on the amount and extent of tracer injected, a possibility that needs to be convincingly ruled out. In an attempt to clarify the results of tracer injections from which intracortical sprouting was inferred (Florence et al., 1998), we compared in the illustrations of the authors the ratio between the spread of tracer at the injection sites in area 1 and the extent of the distribution of retrogradely labeled cells in area 3b (see figure 2 of reference Florence et al., 1998) obtaining results virtually identical in normal monkeys and in monkeys with disrupted somatosensory input from the hand (for extensive studies of corticocortical connectivity between SI fields, see Burton and Fabri, 1995; DeFelipe et al., 1986; Jones et al., 1978). Even assuming that growth of new long-range axons does occur in significant amounts after massive deafferentation, the sprouting hypothesis remains unconvincing on physiological grounds as well. The trigeminal axons reported to sprout into the cuneate nucleus are those normally ending in the adjacent spinal trigeminal nucleus (Jain et al., 2000). These are slow-conducting A-delta and C fibers, known to carry information from pain and temperature receptors (Willis and Westlund, 1997), clearly different from those mediating the fast, low-threshold responses evoked in the reorganized SI by light tactile stimulation (Pons et al., 1991). Moreover, trigemino- and spinothalamic projections have no role in maintaining activity of the somatosensory cortex after lesion (Jain et al., 1997). It should also be added that newly formed dorsal column axons reaching the cuneate nucleus after spinal cord lesion are chronically demyelinated and remain in a pathophysiological state (Tan et al., 2007). Thus, many lines of evidence demand reconsideration of the significance of sprouting in cortical reorganization.

Lane et al. (2008) showed that the reorganization of cortical maps after forepaw amputation in rats does not depend on the sprouting of gracile axons into the denervated cuneate nucleus, an observation in line with recent results from Jain et al. (2008), who, two years after lesioning the cuneate fasciculus at C5−C7 in adult monkeys, observed massive reorganization in SI, finding neurons with face-receptive fields as far medially as the representation of the foot. The foot area receives input from the gracile nucleus via the ventral posterior lateral nucleus of the thalamus (VPL). Based on the sprouting hypothesis, one would expect to find new trigeminal axons terminating in the gracile nucleus. It is significant that, at comparable postlesion times, (p.306) sprouting of spinal trigeminal axons after more massive deafferentations, produced by lesioning both cuneate and gracile fasciculi at higher cervical levels (C3−C5), was limited to the cuneate nucleus (Jain et al., 2000), making it unlikely that cortical reorganization depends solely, or to any significant extent, upon axonal sprouting in the brainstem.

Clinical evidence also does not support sprouting as a leading mechanism of cortical reorganization . In amputees suffering from phantom pain, peripherally or centrally induced analgesia can cause immediate and temporary normalization of cortical maps, with concomitant release from phantom pain (Birbaumer et al., 1997; Huse et al., 2001). Moreover, one patient reported precise, topographically organized phantom sensations after stimulation of the face as early as 24 hours after arm amputation (Borsook et al., 1998). These clinical observations, while not dismissing the possibility of sprouting phenomena occurring at different levels of the somatosensory pathways after deafferentation, question a causal role for newly formed long-range projections in cortical reorganization (Knecht et al., 1998).

If Not Sprouting, Then …

The rapid emergence of phantom sensations and the long-term cortical reorganization occurring after massive deafferentation can be explained by the joint action of two mechanisms: divergence of the normal somatosensory ascending projections and activity-dependent transneuronal atrophy of neurons along the somatosensory pathway from periphery to cortex, with progressive axon withdrawal from deafferented thalamus and cortex.

Divergence in Ascending Somatosensory Projections

At all levels of the somatosensory pathway, the divergence of ascending projections is remarkable. In the medulla oblongata, primary sensory axons from one digit terminate in an elongated field, extending throughout the rostrocaudal extent of the pars rotunda of the cuneate or gracile nucleus, corresponding to a column of approximately 3 × 0.2 mm (Culberson and Brushart, 1989; Florence et al., 1989; Nyberg and Blomqvist, 1982; Rasmusson, 1988). This means that, despite the limited extension of single axonal arborizations, the cumulative input to the cuneate nucleus from a single body part involves thousands of cells, and in any given position approximately 300 peripheral afferents overlap (Weinberg et al., 1990). Such extensive divergence and convergence can readily explain the immediate reorganization of cuneate receptive fields after limited denervation. Divergence of ascending projections is even more dramatic in the thalamus, where a single body part is represented in a lamellar volume of approximately 3 × 3.5 × 0.1 mm and increases exponentially in the thalamocortical projections, where 0.1 mm3 of VPL can project to a cortical area as wide as 20 mm2 (Rausell et al., 1998). This organization implies that the cortical area influenced by a single body part is much larger than that revealed by extracellular multiunit mapping. Thalamic projections to cortical representations of adjacent body parts significantly overlap, providing input to an appropriate cortical representation but overlapping into adjacent (p.307) representations (Snow et al., 1988). Under the conditions of extracellular multiunit mapping, these divergent projections are not seen to drive postsynaptic cells in the inappropriate representation; however, excitatory postsynaptic potentials have been recorded intracellularly from inappropriate cortical neurons after stimulation of adjacent digits (Smits et al., 1991; Zarzecki et al., 1993). Loss of input activity from one digit will unmask these “silent” projections, and stimulation of an adjacent digit with preserved input to the cortex will become effective in driving activity in neurons that have lost peripheral input from an amputated or deafferented digit. By the divergence at each step of the ascending somatosensory pathway, small changes in the input to the brainstem are magnified along their way to the thalamus and cortex and can support large expansions of cortical representations with intact input into regions of SI cortex that have lost input. The underlying anatomical organization provides a basis for the adult CNS to be intrinsically capable of large, activity-dependent changes in the short term. It also explains the observation that a few spared projections, after otherwise massive deafferenting lesions, can maintain a full cortical representation of the deafferented body part (Jain et al., 1997). Divergence also allows for more than 35% of a thalamic representation of a single digit to be destroyed before the cortical representation of that digit begins to shrink (Jones et al., 1997).

There are, however, limitations to divergence-mediated map reorganization. Massive deafferentations, such as amputations or complete dorsal columns lesions, or thalamic lesions involving over 40% of the thalamic volume cause silencing of the SI cortex that lasts for months or years (Jones et al., 1997). This implies that mechanisms other than divergence are needed to account for the emergence of new responses in the deafferented cortex long after massive loss of somatosensory input.

Long-Term Transneuronal Atrophy

An important clue in the search for mechanisms of long-term plasticity in response to massive peripheral or spinal deafferentation comes from studies of the long-term effects of large-scale somatosensory deafferentation in the thalamus of monkeys. Twenty years after cutting spinal dorsal roots C2–T4, the deafferented VPL of the thalamus displays dramatic atrophic changes compared to the normal thalamus, with cells more densely packed, reflecting reduced neuropil mass and loss of lemniscal axons; neuronal somata are shrunken and stain more darkly in Nissl preparations, and there is gliosis (Woods et al., 2000). Such changes are well documented at earlier times in the deafferented cuneate nucleus (Loewy, 1973), but until relatively recently there was no documentation of similar changes in the thalamus. On a larger scale, these changes are reflected in a conspicuous volume reduction of the deafferented VPL. Such physical rearrangement causes the face representation, normally contained within the boundaries of the ventral posterior medial nucleus, to collapse into the deafferented hand representation in VPL, so that cells with receptive fields on the face lie adjacent to cells with receptive fields on the foot (Jones and Pons, 1998), a proximity never observed in the normal thalamus, where face and foot representations are separated by the large representation of the hand (Jones, 2007).

(p.308) Two aspects of the transneuronal atrophic process are especially important in relation to long-term cortical reorganization. First, both in brainstem and thalamus, actual cell loss by death of neurons is small, not more than 15% of the cells in the cuneate nucleus and even fewer in the thalamus disappearing 20 years after deafferentation (Woods et al., 2000).Thus, the majority of the cells undergoing primary (in the cuneate nucleus) and secondary (in the thalamus) transneuronal atrophy do survive and may be able to drive postsynaptic activity in the reorganized cortex, because in patients with long-standing amputations who underwent neurosurgery, electrical stimulation of the deafferented thalamus elicited clear sensations in the missing limb (Davis et al., 1998). Second, the process leading to secondary transneuronal atrophy in the thalamus is progressive and extremely slow. It begins to become identifiable 10 years after deafferentation, and more than 10 years is necessary for cellular changes to reach their fullest observed extent (Woods et al., 2000). The slow, progressive but inexorable shrinkage of neurons and withdrawal of their axons from thalamus and cortex may represent a powerful stimulus to reorganization under conditions of long-term deafferentations, and the physical proximity of face and foot representations in the deafferented thalamus should facilitate the synaptic rearrangement of intact divergent projections mediating the expansion of the cortical face representation into the neighboring silenced cortex. This has profound clinical implications. In amputees and patients with spinal cord lesions, phantom sensations and central pain can emerge years after the deafferenting injury (Hill, 1999; Stormer et al., 1997), and an atrophic process unfolding at such a slow pace is the only plausible mechanism that can explain the late appearance of signs of deafferentation-induced thalamic and cortical reorganization.

Transneuronal Atrophy in the Short Term

While the slow progression of transneuronal atrophy represents an important potential mechanism of long-term cortical plasticity and its clinical manifestations, it has not been without its detractors. They have sought to minimize the role of transneuronal atrophy in cortical plasticity, reasoning that clinical symptoms associated with massive deafferentations usually take much shorter than 10 years to emerge and, in many cases, cortical reorganization takes place in the absence of any microscopic sign of atrophy at any level of the central somatosensory pathways (Kaas and Florence, 2001; Kaas et al., 2008; Merzenich, 1998). These arguments, however, fail to recognize the progressive nature of activity-dependent transneuronal atrophy and do not take into account the likelihood that the axon of a deafferented cuneate or thalamic neuron may be undergoing changes long before shrinkage of its cell body becomes microscopically visible. The inexorable progression of transneuronal atrophy in the years after cell body atrophy becomes identifiable strongly suggests that its action is already affecting the deafferented neurons along the somatosensory pathway well before. In order to verify this, it was essential to look at the axons themselves of deafferented neurons to determine whether they were in fact withdrawing from higher centers before the detection of shrinkage of their parent somata.

(p.309) We investigated this issue (Graziano and Jones, 2009) by using a quantitative approach. We studied morphological changes in a large population of lemniscal and thalamocortical axons two years after complete transection of the cuneate fasciculus at the level of the first cervical segment in adult monkeys. Two years is almost a decade before cell body shrinkage and gliosis can be identified in the thalamus (Woods et al., 2000). We examined the morphology of axons of cuneate neurons terminating in the thalamus and of thalamic axons terminating in the cortex by injection of anterograde tracers in the cuneate nucleus or thalamus and collected data from more than 15 miles of axon reconstructions in physiologically identified regions of thalamus and cortex, obtaining two important results.

Two years after complete cuneate fasciculotomy, the deafferented regions in the brainstem, thalamus, and cortex were virtually silent, with no detectable expansion of the adjacent face representation. The lack of frank expansion of the face representation in our experiments sug-gests that early cortical map reorganization, reported by other studies after lesion of the dorsal columns at levels varying from C3 to C7 (Jain et al., 1997; Jain et al., 2008), may depend on preserved input from upper cervical segments. Because of the overlap of cuneate and trigeminal innervation of the neck and the chin (see above), lesions at or below the C3 level will preserve input from this part of the face in the cuneate nucleus. By interrupting the cuneate fasciculus at C1, we effectively removed all input to the cuneate nucleus, resembling the massive denervation performed by cutting the dorsal roots from C2 to T4 (Pons et al., 1991). After deafferentation of this extent, the area of cortex receiving cuneate input is completely silenced (Bioulac and Lamarre, 1979), with the exception of a small region receiving head input behind the arm representation, present in normal monkeys (Dreyer et al., 1975; Ullrich and Woosley, 1954). Unfortunately, the only available data on cortical reorganization from 6 to 8 months to 2 years and thus relevant to our discussion were obtained after lesions at levels ranging from C3 to C7, so they do not shed light on this issue. It must be noted that even after more restricted deafferentations of single digits, areas of silenced cortex persist for as long as 32 weeks, and the extent of cortical reactivation at this time depends on the size of the deafferenting lesion (Darian-Smith and Ciferri, 2006). These observations suggest that after complete cuneate deafferentation, thalamic and cortical hand representations may remain silent for years before becoming occupied by inputs from the face.

The second, more important result of our study is that transneuronal atrophy affected the morphology of second-order lemniscal and third-order thalamocortical axons long before overt shrinkage of their deafferented parent cells could be identified in dorsal column nuclei or thalamus (Graziano and Jones, 2009). The effects of the two-year-long deafferentation on the terminal arbors of axons in thalamus and cortex were similar, consisting primarily of a considerable reduction in size and number of synaptic boutons (see figure 24.1, plate 12).

The inability to detect transneuronal atrophy in earlier studies of peripheral deafferentation is the consequence of focusing only on somal morphology. Our results demonstrate that even at relatively early postlesional stages, transneuronal atrophy has affected lemniscal and (p.310)

Subcortical Contributions to Cortical Reorganization after Massive Somatosensory Deafferentation

Figure 24.1 (plate 12) Diagram summarizing the morphological changes of withdrawing lemniscal axons (blue) from the upper limb and upper trunk representations in VPL after transection of the cuneate fasciculus. The same scheme applies to thalamocortical axons withdrawing from the upper limb and upper trunk representation in the somatosensory cortex. The first signs of transneuronal atrophy are a reduction in size and number of synaptic boutons, the presence of incomplete endings, and a loss of short terminal branches. The divergent projections of normal axons (red) from face and lower body representations to the adjacent cuneate representations, normally unable to drive activity, constitute the basis for the expansion of the silenced upper limb/upper trunk representation by adjacent representations of the face and lower body. In the long term, transneuronal atrophy, with shrinkage and loss of deafferented neurons, enhances the expansion of representations with intact innervation. From Graziano and Jones (2009).

thalamocortical axon terminations, suggesting that transneuronal atrophy and withdrawal of the axons of deafferented neurons from centers higher in the somatosensory pathway is likely to contribute to cortical reorganization. Even in the short term, and even after deafferenting peripheral injuries that are not commonly thought to induce loss of dorsal root ganglion cells (Kaas and Florence, 2001), there may be withdrawal of primary afferents from the dorsal column nuclei. Indeed, limb amputations or transections of nerves which sever the peripheral axons of dorsal root ganglion cells do cause extensive loss of dorsal root ganglion cells and of sensory axons entering the brainstem and spinal cord (Csillik et al., 1982; Knyihar-Csillik et al., 1987; Liss et al., 1996; Liss and Wiberg, 1997a; 1997b). Moreover, this is accompanied by transneuronal atrophy of neuronal somata in the cuneate nucleus and thalamus (Florence and Kaas, 1995; Jones and Pons, 1998; Woods et al., 2000), and in humans there is a decrease in thalamic gray matter demonstrable by magnetic resonance imaging (Draganski et al., 2006). The atrophy of cuneate cell bodies will be accompanied by changes of the type we have described in their (p.311) axons terminating in the thalamus and transynaptically in the axons of deafferented thalamic relay neurons in the cortex. Thus, peripheral and central deafferentation may act through the same mechanisms.

Transneuronal Atrophy Commences Very Early

Mechanisms of central plasticity that depend upon transneuronal effects upon the axonal terminations of deafferented neurons may come into play even before morphological changes become evident in the axonal terminations. Two months after unilateral cuneate fasciculotomies in adult monkeys, we studied differential gene expression in the deafferented regions of brainstem, thalamus, and cortex (Graziano and Jones, 2006). Analysis of the biological functions associated with up- or downregulated genes showed a clear overrepresentation of genes associated with neuronal atrophy, neurodegeneration, and neuroinflammation. In adjacent regions, in which representations receiving inputs from the face and lower limb were located and which expand to occupy the deafferented regions, we also found upregulated genes associated with positive plasticity, such as neurogenesis, synaptogenesis, and short- and long-term synaptic plasticity. These findings imply that, even at very early stages after denervation, activity-dependent transneuronal changes are already affecting neurons and their terminations along the somatosensory pathway. The many intracellular metabolic pathways that are up- or downregulated under these conditions may lead not only to axon withdrawal and cell atrophy in the short and long term but also to the synaptic plasticity necessary to mediate the early and late changes in the receptive field properties of cells that lead to cortical map reorganization.

The evidence that somatosensory denervation induces early regulation of genes related to neuronal atrophy, together with progressive atrophic changes, first involving axon terminals and synapses, and later causing axon withdrawal and cell body atrophy and death in thalamus and cortex, suggests that a neurodegenerative process leading to anatomical and functional reorga-nization of thalamus and cortex at all stages of peripheral and central deafferentations likely to be a powerful inducement of representational plasticity.


We thank Phong Nguyen for technical support and Prabhakara Choudary and Karl Murray for advice. This work was supported by grant number NS21377 from the National Institutes of Health, United States Public Health Service.

Subcortical Contributions to Cortical Reorganization after Massive Somatosensory Deafferentation

Plate 12 (figure 24.1) Diagram summarizing the morphological changes of withdrawing lemniscal axons (blue) from the upper limb and upper trunk representations in VPL after transection of the cuneate fasciculus. The same scheme applies to thalamocortical axons withdrawing from the upper limb and upper trunk representation in the somatosensory cortex. The first signs of transneuronal atrophy are a reduction in size and number of synaptic boutons, the presence of incomplete endings, and a loss of short terminal branches. The divergent projections of normal axons (red) from face and lower body representations to the adjacent cuneate representations, normally unable to drive activity, constitute the basis for the expansion of the silenced upper limb/upper trunk representation by adjacent representations of the face and lower body. In the long term, transneuronal atrophy, with shrinkage and loss of deafferented neurons, enhances the expansion of representations with intact innervation. From Graziano and Jones (2009).


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