THE JOURNAL OF COMPARATIVE NEUROLOGY 485:64 –74 (2005)

Plasticity of the Cortical Dentition Representation after Tooth Extraction in Naked Mole-Rats ERIN C. HENRY,1 PAUL D. MARASCO,1 AND KENNETH C. CATANIA2* Neuroscience Graduate Program, Vanderbilt University, Nashville, Tennessee 37235 2 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235 1

ABSTRACT Naked mole-rats (Heterocephalus glaber) have a large cortical representation of their behaviorally important front teeth, accounting for 30% of primary somatosensory cortex (SI). Here we investigated the plasticity of this dental representation after the extraction of a single lower tooth. The representation of the contralateral lower incisor normally accounts for ⬃15% of somatosensory cortex in mole-rats. In five mole-rats the lower right incisor was extracted on either postnatal day 7 or 21. After 5– 8 months the deprived tooth zone in S1 was investigated with multiunit microelectrode recordings. The results revealed a dramatic reorganization of the orofacial representation in SI. Neurons in the cortical lower tooth representation were responsive to tactile inputs from surrounding orofacial structures, including the contralateral upper incisor, ipsilateral lower incisor, tongue, chin, gums, and buccal pad. Neurons in the former lower tooth zone had complex receptive fields that often encompassed multiple sensory surfaces surrounding the extracted tooth in the periphery. These results suggest that the representation of the dentition in mammals is capable of significant reorganization after the loss of sensory inputs from the teeth. These data parallel findings in the somatosensory hand area of primates after deafferentation where cortex can become activated by a mixture of widely spaced surrounding sensory surfaces (e.g., chin and upper arm). J. Comp. Neurol. 485:64 –74, 2005. © 2005 Wiley-Liss, Inc. Indexing terms: somatosensory; teeth; dental; neocortex; phantom

Despite extensive investigations of somatosensory cortex in mammals, surprisingly few studies have explored the cortical representation of the dentition. The sensory representation of teeth may have been largely overlooked because it is difficult to expose these representations at the rostrolateral extreme of cortex (see Jain et al., 2001; Remple et al., 2003) and difficult to stimulate oral structures when using stereotaxic equipment that holds or blocks the teeth. Yet masticating food is a complex process requiring fine sensory discriminations integrated with motor patterns and the obvious survival value of this behavior suggests that the dentition and associated oral structures should have a large representation in somatosensory cortex. A number of recent investigations support this suggestion. For example, Jain et al. (2001) explored the representations of the dentition and associated oral structures in somatosensory cortex of New World monkeys and reported that nearly one-third of area 3b was devoted to these representations. In addition, Disbrow et al. (2003) described unique integration of oral inputs across the midline in humans that may be related to © 2005 WILEY-LISS, INC.

speech. Recently, the representation of the incisors and tongue has been identified in laboratory rats (Remple et al., 2003) and a substantial area of previously unexplored rostrolateral cortex was found to represent the dentition. In naked mole-rats (Fig. 1), which use their specialized teeth to excavate tunnels and manipulate objects, ⬃30% of primary somatosensory cortex is devoted to the two contralateral front teeth (Catania and Remple, 2002; and see Fig. 2).

Grant sponsor: National Science Foundation Career Award; Grant number: 0238364; National Institutes of Health; Grant number: R21 DE014739 (to K.C.C.). *Correspondence to: Kenneth C. Catania, Department of Biological Sciences, Vanderbilt University, VU Station B, 351634, Nashville, TN 37235. E-mail: [email protected] Received 30 April 2004; Revised 26 October 2004; Accepted 23 December 2004 DOI 10.1002/cne.20511 Published online in Wiley InterScience (www.interscience.wiley.com).

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65 rats because this species depends heavily on its incisors for a number of behaviors and has a particularly large primary somatosensory cortex (S1) dominated by the representation of the dentition (Catania and Remple, 2002). To investigate the potential plasticity of these representations, the lower right front incisor was extracted in juvenile naked mole-rats (age 7 and 21 days) and the deprived cortical area was investigated with microelectrode recordings after survival times of 5– 8 months. We found that removal of a single lower incisor in juvenile mole-rats resulted in substantial reorganization of the dental representation. After several months, the deafferented lower incisor representation was activated throughout its entire extent by a mixture of sensory surfaces close to the mouth in the periphery. These results are similar to those previously reported for the somatosensory hand area of primates after deafferentation, where cortex is often reactivated by a mixture of widely spaced surrounding sensory surfaces, such as the chin and upper arm (Yang et al., 1994; Jain et al., 1997; Florence et al., 2000). Potential mechanisms of cortical reorganization and the possible consequences for sensory perceptions are discussed.

MATERIALS AND METHODS Fig. 1. A normal mole-rat compared to a tooth extraction case. A: An adult mole-rat. Note the incisors, which remain outside the mouth when it is closed. B: Front view of a control mole-rat. C: Front view of a mole-rat that had its lower right incisor removed at postnatal day 7. Scale bars ⫽ 2 cm in A; 5 mm in B,C.

Fig. 2. Results of microelectrode recordings in a control mole-rat, showing the extent of primary somatosensory cortex and the representations of the different body parts (adapted from Catania and Remple, 2002). Dots represent individual electrode penetrations. Stars indicate microlesion sites. X’s correspond to no-response sites. S2/PV, secondary somatosensory area/parietal ventral area. Scale bar ⫽ 1 mm.

It seems likely from these studies that the representation of the dentition occupies a relatively large extent of somatosensory cortex in mammals generally. Given the behavioral importance of teeth and their substantial representation in the cortex, we wondered how these representations might be altered by the deafferentation that accompanies tooth loss (Linden and Scott, 1989). We chose to examine the reorganization of the dental representations in naked mole-

Five naked mole-rats (Heterocephalus glaber) were used in this study. All animal procedures followed National Institutes of Health guidelines and were performed according to the standards set by the Animal Welfare Act and the Vanderbilt University Institutional Animal Care and Use Committee. Naked mole-rats are in the family Bathyergidae and are unique in having a colony structure similar to the social insects. Young are weaned at roughly 3– 4 weeks and may live over 20 years in captivity (Jarvis, 1991). For our experiments, each mole-rat had a single, lower right incisor extracted (Fig. 1) at either postnatal day 7 (P7, three animals) or 21 (P21, two animals). We chose to perform these extraction studies using young mole-rats because the lower incisor is difficult to extract in adult rodents without damaging the mandible (Yonehara et al., 2002). In addition, it is difficult to examine cortical plasticity related to the upper incisor generally, because its representation in lateral cortex (Catania and Remple, 2002) merges with the upper incisor representation in other, lateral cortical areas (S2 and PV), making interpretation of reorganized maps problematic. Finally, the more medial position of the lower incisor in the primary somatosensory cortex makes it more accessible than the upper incisor representation (Remple et al., 2003). For these reasons our initial studies of plasticity in cortical dental representations have been carried out in juveniles, well past the time of tooth eruption (Jarvis, 1991), and at an age that is generally considered to be past the early critical period of rodent development (ending at P4 –5; see Killackey et al., 1990; Woolsey, 1990). The mole-rats were anesthetized with 4% isoflurane to induce a surgical plane of anesthesia. The lower tooth was extracted using serrated tweezers, after which topical antibiotics were applied. After 5– 8 months the animals were anesthetized with 15% urethane diluted in distilled water at a dosage of 1.5 g/kg. Body temperature was maintained with a heating pad and hot water bottles. A headpost was attached to the right side of the skull using dental cement and a craniotomy was performed to expose the left cortex. The cortex was covered with silicon and a digital photo-

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Figure 3

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Fig. 3. Results of microelectrode recordings from case 03-06, a 5-month-old mole-rat that had a lower right incisor removed at postnatal day 7. A: The gray regions illustrate the boundaries of the body part representations in SI. The rostral outlined crescent (dashed line) corresponds to the reorganized, former lower incisor representation. Dots represent individual electrode penetrations. Stars indicate microlesion sites. X’s correspond to no-response sites. B: Expanded sec-

tion of panel A showing the penetration sites mapped in the former lower incisor area during the recording. Each reorganized site is numbered and corresponds to a receptive field diagram in panel D. C: Labeled microlesions related to the cytochrome oxidase-stained flattened section of cortex. D: Diagrams of the receptive fields for each penetration site numbered in panel B. Scale bars ⫽ 1 mm in A–C.

graph of the cortical surface was taken in order to mark penetration sites during the recording session. Multiunit recordings were performed using low impedance tungsten electrodes (1.0 M⍀ at 1,000 Hz) at cortical depths ranging from ⬃400 –500 ␮m. One investigator was responsible for positioning the electrode in each cortical site and the second investigator identified the receptive fields for each penetration and was thus blind to the location of the recording electrode in the brain. The same recording method was used to map the control animals (previously published in Catania and Remple, 2002). Soft probes and calibrated von Frey hairs were used to identify the receptive fields for each penetration. The boundary of the receptive field was defined as the skin surface or tooth surface where light contact produced a detectable increase in neural activity as visualized by an oscilloscope combined with auditory monitoring through a speaker. The same procedures were used in previously published control cases (Catania and Remple, 2002). Each identified

receptive field was drawn onto a schematic of a mole-rat body. A total of 1,070 penetration sites were mapped in the five cases. Selected electrode penetrations were marked with a microlesion (10 ␮A while retracting from a depth of 1,000 ␮m at a speed of 70 ␮m/s). The animal was then given an overdose of sodium pentobarbital and perfused with 0.9% saline followed by 4% paraformaldehyde. The brain was removed and the cortex was flattened between glass slides. The cortices were immersed in 30% sucrose in phosphate buffer for 12 hours and flattened sections were cut on a freezing microtome at 50 ␮m. Sections were processed for the metabolic enzyme cytochrome oxidase. The recording sites marked on the photograph of the brains were aligned with the cortical sections using microlesions. Sections were photographed using a 35-mm digital camera, or digital “Spot” Camera (Diagnostic Instruments, Sterling Heights, MI) mounted to a microscope. Image contrast was adjusted using the levels function in PhotoShop 7 (Adobe, San Jose, CA). Digital files

Figure 4

PLASTICITY OF CORTICAL DENTITION were then transferred to Adobe Illustrator using the “Place” command and finally exported as Tiff files.

RESULTS Our results revealed a large-scale reorganization of the somatosensory face representation following tooth extraction in naked mole-rats. This can be best appreciated by first considering the normal organization of dental areas in mole-rat somatosensory cortex. Figure 2 shows one of our control animals (see Catania and Remple, 2002, for more details) and illustrates the large area of rostrolateral cortex taken up by the lower incisor representation. In contrast to normal animals, the region of cortex representing the lower incisor in all of our tooth extraction cases was activated across its entire rostrocaudal extent by a mixture of surrounding oral-facial structures. These included contralateral upper incisor, ipsilateral lower incisor, tongue, chin, gums, and buccal pad (all receptive fields are contralateral unless otherwise noted). At many electrode penetrations neurons had complex receptive fields that included multiple sensory surfaces adjacent to the extracted tooth, served by both the mandibular and maxillary divisions of the trigeminal nerve. In case 03-06 (Fig. 3), the lower incisor was extracted at 1 week of age and the former tooth representation was activated by a number of adjacent structures, the most prominent of which were the ipsilateral lower incisor (30 penetration sites), tongue (23 sites), upper incisors (22 sites), and buccal pad (14 sites). There was a scattered distribution of neurons responsive the stimulation of the ipsilateral lower incisor throughout the representation and at each of these sites, with one exception, the receptive fields included other orofacial sensory structures (for selected examples, see Fig. 3, penetrations 1, 7, 14, 27, 49). The rostrolateral-most portion of the representation was largely activated by neurons responsive to the tongue. The tongue representation normally lies rostral to the lower incisor area in a discrete anterior-lateral position along the rostrolateral border of SI (Fig. 2). However, in case 03-06 responses to the tongue were found throughout the majority of the area normally occupied by the lower incisor. Many of these penetration sites were also responsive to other orofacial body parts forming complex mixtures of receptive fields (see Fig. 3, penetrations 7, 10, 13, 17–21, 29, 31, 34, 37, 41, 45, 47). In the lateral portion of the former incisor representation there was also an area responsive to the chin. This set of responses was isolated

Fig. 4. Results of microelectrode recordings from case 03-03, an 8-month-old mole-rat that had a lower right incisor removed at postnatal day 21. A: The gray regions illustrate the boundaries of the body part representations in SI. The rostral outlined crescent (dashed line) corresponds to the reorganized, former lower incisor representation. Dots represent individual electrode penetrations. Stars indicate microlesion sites. X’s correspond to no-response sites. B: Expanded section of panel A showing the penetration sites mapped in the former lower incisor area during the recording. Each reorganized site is numbered and corresponds to a receptive field diagram in panel D. C: Labeled microlesions related to the cytochrome oxidase-stained flattened section of cortex. Note the far rostral lesion sites and their relation to the cytochrome dense areas of SI face representations. D: Diagrams of the receptive fields for each penetration site numbered in panel B. Scale bars ⫽ 1 mm in A–C.

69 from the normal SI representation of the chin by the buccal pad representation and the receptive fields for each of these chin sites contained at least one other body surface (for examples, see Fig. 3, penetrations 36, 38, 41– 43). Neurons in the medial portion of the former lower incisor representation were activated by stimulation of the upper incisor. This medial upper incisor representation was separate from the lateral upper incisor representation (Fig. 3, penetrations 2– 6, 8, and 9), and neurons at the lateral border of this area had complex receptive fields that included the tongue, chin, and ipsilateral lower incisor (e.g., Fig. 3, penetrations 7, 10, 13, 15, 17, 18). In case 03-06, the buccal pad representation, which normally lies caudal to the lower incisor representation, expanded rostrally into the deactivated area, dividing the “new” medial upper incisor responses from the normal, lateral upper incisor representation (Fig. 3, penetrations 22, 23, 18, 20, 30). In some places the buccal pad expansion extended to the rostral extreme of the deactivated lower incisor representation (Fig. 3, penetrations 22, 23, 29, 30). Thus, representations that flanked both the rostral (tongue) and caudal (buccal pad) portions of the former incisor representation expanded in opposite directions to fill the entire deafferented zone. Results were similar for the other cases, although the details of the activation pattern varied. For example, activation of the lower incisor region in case 03-03 (Fig. 4; tooth extracted at 3 weeks of age) was dominated by a rostral expansion of the buccal pad (39 penetration sites were responsive to buccal pad). As in case 03-06, the buccal pad expanded to fill the far rostral extent of the deafferented tooth zone (for progression, see Fig. 4, penetrations 20 –23). In addition to the buccal pad extension in case 03-03, the tongue representation also expanded considerably in the caudolateral (Fig. 4, penetrations 50, 53, 55) and caudomedial directions (Fig. 4, penetrations 30, 36, 42, 43), where sites responded to a mixture of the tongue, upper incisor, and ipsilateral lower incisor. A small patch of upper incisor responses was identified in a discrete medial zone (Fig. 4, penetrations 8, 9), and a number of penetrations throughout the representation responded to the ipsilateral lower incisor (e.g., Fig. 4, penetrations 15, 19, 29, 35, 42, 56). In both case 03-06 and case 03-03, neurons at numerous electrode penetrations had complex receptive fields where neurons responded to stimulation of multiple sensory surfaces (e.g., Fig. 4, penetrations 42, 53, 55). In case 03-04, tooth-extraction was at 3 weeks of age and expansion of the upper incisor representation dominated the reorganized cortex after 7 months (Fig. 5). There were 21 penetration sites where neurons responded to stimulation of the upper incisors. At many of these sites neurons were also responsive to other structures, such as the ipsilateral lower incisor (Fig. 5, penetrations 21, 23), the buccal pad (Fig. 5, penetration 34), and the chin (Fig. 5, penetration 12). As in the other cases, there was a cluster of upper incisor responses in the rostromedial portion of the representation (Fig. 5, penetrations 4 and 8) that was isolated from the normal, more lateral upper incisor responsive area. In case 03-05 the lower incisor was extracted at 1 week of age, and there was a more even and overlapping expansion of tongue, buccal pad, upper incisor, gums, and ipsilateral lower incisor representations (Fig. 6). The tongue was a major component of this activation (e.g., Fig. 6,

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Figure 5

PLASTICITY OF CORTICAL DENTITION penetrations 11, 22, 24, 32) occupying the lateral portion of the former incisor representation and stretching the length of the rostral– caudal axis of the former lower incisor representation. There were also isolated patches of buccal pad responsive cells throughout the representation (Fig. 6, penetrations 2, 13, 25) and a medial upper incisor responsive area (Fig. 6, penetration 1). In every case many penetration sites were responsive to multiple sensory surfaces and a subset of electrode penetrations contained neurons that were coactivated by facial structures that are usually widely separated in the cortical representation by the intervening representation of the lower incisor. For example, in case 03-06 there were some sites responsive to both (but not necessarily exclusively) the tongue and buccal pad (Fig. 3, penetrations 13, 29), the tongue and both the upper and ipsilateral lower incisors (Fig. 3, penetrations 17, 18, 35, 51), and the chin and buccal pad (Fig. 3, penetrations 30, 31). In cases 03-03 and 03-05, there were also sites responsive to the tongue, upper incisors, and ipsilateral lower incisors (Fig. 4, penetrations 53, 55; Fig. 6, penetrations 4, 9, 32). Similar but fewer coactivated sites were observed in case 03-04 (e.g., Fig. 5, penetrations 1–3, 12). Clearly, an expanded representation of the orofacial sensory surfaces adjacent to the deafferented lower incisor was pervasive. However, many penetration sites (93) were also identified where neurons in the deactivated area had become responsive to stimulation of the ipsilateral lower incisor (Figs. 3– 6). This was not found in the control cases previously explored (Fig. 2, and see Catania and Remple, 2002). The ipsilateral lower incisor responses were usually at sites containing complex receptive fields that included multiple areas on the face. For example, receptive fields often included the ipsilateral lower incisor with either the upper incisor, the tongue, or the buccal pad, and receptive fields often included the ipsilateral lower incisor with a combination of these sensory surfaces.

Relationship of CO pattern to mapping results After each experimental case, electrolytic microlesions were made in cortex to mark important electrode penetration sites throughout the SI body representation and former incisor area (Figs. 3– 6). These lesions were usually placed at the boundaries of the SI representation in order to highlight the extent of the representation that produced positive neuronal responses to peripheral stimulation. These lesions allowed for alignment of the physiological data with the cortical tissue after it had been flattened, sectioned, and processed for cytochrome oxidase (CO). By aligning the tis-

Fig. 5. Results of microelectrode recordings from case 03-04, an 8-month-old mole-rat that had a lower right incisor removed at postnatal day 21. A: The gray regions illustrate the boundaries of the body part representations in SI. The rostral outlined crescent (dashed line) corresponds to the reorganized, former lower incisor representation. Dots represent individual electrode penetrations. Stars indicate microlesion sites. X’s correspond to no-response sites. B: Expanded section of panel A showing the penetration sites mapped in the former lower incisor area during the recording. Each reorganized site is numbered and corresponds to a receptive field diagram in panel D. C: Labeled microlesions related to the cytochrome oxidase-stained flattened section of cortex. D: Diagrams of the receptive fields for each penetration site numbered in panel B. Scale bars ⫽ 1 mm in A–C.

71 sue reacted for CO with the physiological data, we were able to confirm the boundaries of the CO-dense SI body representation and show that the orofacial representations (particularly the chin and buccal pad) had in fact expanded their boundaries beyond the CO-dense pattern that normally marks the boundary of their representation (Fig. 7). Case 03-03 provided the best example of CO patterning in the SI body representation, showing that the orofacial responses activating the former incisor representation were rostral and medial to the boundary of the normal buccal pad and chin representations (Fig. 7). Although we did not observe gross differences between the activation patterns after tooth removal at 7 or 21 days, there were some subtle trends. Cases 03-06 and 03-05, in which teeth were extracted at 1 week of age, both had prominent expansions of the tongue representation, which played a major role in activating the former incisor area. These two cases also had a greater number of complex receptive fields compared to the 3-week extraction cases. The younger age group had receptive fields that often contained penetration sites responsive to three or more different sensory surfaces on the face (e.g., Fig. 3, penetrations 17, 19, 30; Fig. 6, penetrations 4, 11, 23). Cortex in the 3-week-old toothextraction cases (cases 03-03 and 03-04), was largely activated by representations caudal to the former incisor area (specifically, the buccal pad representation for case 03-03 and the upper incisor representation for case 03-04).

DISCUSSION Teeth are important to the survival of nearly every mammal species and the complexity of the process of mastication suggests that dental afferents should have a prominent representation in cortex. This has been confirmed in a number of recent investigations (see Jain et al., 2001, for primates; Catania and Remple, 2002, for mole-rats; and Remple et al., 2003, for rats). What happens when afferents to this territory of cortex are lost? We have begun to investigate this question by examining tooth loss in naked mole-rats because they have a particularly large and accessible cortical representation of their behaviorally important front teeth. Here we report that large areas of the cortical dental representation devoted to an extracted incisor were activated by surrounding sensory structures after 5– 8 months. Our results are summarized in Figure 8, which shows the large lower incisor representation and the orofacial sensory surfaces that activate this region following tooth extraction. In each of the cases the entire extent of the deprived incisor representation was activated by surrounding sensory surfaces. This activation pattern consistently included expansions of surrounding representations that were both rostral (the tongue) and caudal (buccal pad, upper incisors, chin) to the former incisor representation. The caudal expansion of the tongue representation played a major role in the younger age group (P7 tooth-extraction cases), while the rostral expansion of several facial representations (e.g., buccal pad, chin, upper incisor) was the major component in the older age group (P21 tooth-extraction cases). The small number of animals used in each age group does not allow us to make strong conclusions about these potential differences. However, in every case there were many electrode penetrations where neurons had complex receptive fields. It seems significant that the complex receptive fields characterizing the deprived tooth zone in mole-rats are similar to those noted in the reorganized hand areas of long-standing limb deafferentation cases (Jain

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Figure 6

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et al., 1997; Florence et al., 2000). These receptive fields are in turn similar to the multiple areas of the body that may generate referred, phantom limb sensations reported by patients (Ramachandran et al., 1992; Ramachandran and Hirstein, 1998; Ramachandran and Rogers-Ramachandran, 2000). An additional consistent finding was the presence of an isolated pocket of upper incisor responsive neurons in the far medial portion of the former incisor representation. This pocket of responses was isolated from the rostral expansion of the upper incisor representation in the more lateral portions of the former incisor area. Finally, many of the sites in the reactivated area were responsive to stimulation of the ipsilateral lower incisor. Tract-tracing studies in laboratory rats have revealed sparse subcortical fiber pathways providing ipsilateral trigeminal afferents to SI, and this could account for the activation of dental areas by ipsilateral areas of the face in our experimental cases (Pfaller and Arvidsson, 1988; Jacquin et al., 1990a,b; Marfurt and Rajchert, 1991). However, in control cases (Catania and Remple, 2002) no sites in the lower tooth representation were identified that responded to ipsilateral stimulation of the face. Perhaps relatively weak ipsilateral inputs were strengthened when the contralateral incisor was extracted. Another possible source for the ipsilateral responses could be from callosal connections. It is possible that strengthened inputs from callosal connections could contribute to the activation of deprived cortex corresponding to midline structures, which have been shown to have particularly dense callosal connections (Manzoni et al., 1980, 1989; and see Disbrow et al., 2003). This possibility may not have been addressed in many previous investigations of cortical plasticity following deafferentations, as the distal structures (limbs) investigated tend to have relatively much fewer callosal connections. Two predominant mechanisms have been suggested for the reactivation of cortical areas following deafferentation— unmasking of latent inputs and the sprouting of new connections at cortical or subcortical levels. Either of these mechanisms seems possible for the reorganized lower incisor representation in naked mole-rats. However, because we examined plasticity in juvenile mole-rats, another possibility is that we induced the widespread branching of thalamocortical axons during development, and this activation pattern was maintained and strengthened in adults (for example, Catalano et al., 1995). It is also possible that thalamocortical fibers normally branch widely across somatosensory areas in mole-rats, providing a potential source of activation of the lower incisor representation following deafferentation through the unmasking of normally silent afferents (e.g., Schroeder et al., 1995; Garraghty and Muja, 1996). Deter-

Fig. 6. Results of microelectrode recordings from case 03-05, a 5-month-old mole-rat that had a lower right incisor removed at postnatal day 7. A: The gray regions illustrate the boundaries of the body part representations in SI. The rostral outlined crescent (dashed line) corresponds to the reorganized, former lower incisor representation. Dots represent individual electrode penetrations. Stars indicate microlesion sites. X’s correspond to no-response sites. B: Expanded section of panel A showing the penetration sites mapped in the former lower incisor area during the recording. Each reorganized site is numbered and corresponds to a receptive field diagram in panel D. C: Labeled microlesions related to the cytochrome oxidase-stained flattened section of cortex. D: Diagrams of the receptive fields for each penetration site numbered in panel B. Scale bars ⫽ 1 mm in A–C.

Fig. 7. An example of the relationship between cytochrome oxidase modules representing the body part representation in SI and the location of physiologically placed microlesions made during the recording session for case 03-03. A: The cytochrome oxidase reacted cortical tissue with labeled microlesions. B: The SI body representation has been outlined to show the boundary of the area as compared to the location of the microlesions. C: The individual electrode penetrations have been aligned with the tissue to show the extent of the rostral reorganized incisor area. BP, buccal pad; FL, forelimb; HL, hindlimb; LI, lower incisor; To, tongue; Tr, trunk; UI, upper incisor. Scale bar ⫽ 1 mm in C (applies to A–C).

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Fig. 8. Summary of our results illustrating normal somatosensory cortex in naked mole-rats and the large representation of the lower incisor (top panel). Five to eight months after the lower incisor was extracted, neurons in the tooth representation were activated by surrounding sensory surfaces on the face (lower panel). Scale bars ⫽ 1 mm.

mining the mechanisms underlying the reorganization of cortical dental representations could provide insight into the relatively common phenomenon of phantom tooth pain (Marbach et al., 1982; Bates and Stewart, 1991; Marbach, 1993; Tassinari et al., 2002).

ACKNOWLEDGMENTS The authors thank Fiona Remple and Jon Kaas for helpful comments on the research and article. We also thank Justin O’Riain for providing mole-rats and for support and guidance in their care and maintenance.

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