Non-invasive stimulation of the vibrissal pad improves recovery of whisking function after simultaneous lesion of the facial and infraorbital nerves in rats

We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation; Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the amplitude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate.     

Persistence of vibrissal motor representation following vibrissal pad deafferentation in adult rats

The effect of sensory vibrissal pad denervation on M1 organization was studied in adult rats 2 weeks after the infraorbital nerve was severed. Cortical motor output organization was assessed mapping the representation size and thresholds of vibrissa movements evoked by intracortical electrical microstimulation (ICMS). Motor cortex output patterns of control and sham groups of rats were compared with those of rats that had received unilateral or bilateral infraorbital nerve lesions. The mean size of the vibrissa representation in both unilateral and bilateral input-deprived hemispheres was not significantly different from those in control and sham hemispheres. The mean threshold required to evoke vibrissa movements was significantly higher in both groups of deafferented hemispheres than in control and sham groups of hemispheres. In contrast, the mean threshold required to evoke other types of movements from both groups of input-deprived hemispheres were similar to those found in the control and sham groups of hemispheres. These results indicate that input-deprived vibrissal motor representation reflects lower-than-normal excitability, although the size and topographic relationship with neighboring representations are normal.     

Spontaneous rhythmic field potentials of isolated mouse hippocampal–subicular–entorhinal cortices in vitro

It has been proposed that abnormal vibrissae input to the motor cortex (M1) mediates short-term cortical reorganization after facial nerve lesion. To test this hypothesis, we cut first the infraorbital nerve (ION cut) and then the facial nerve (VII cut) in order to evaluate M1 reorganization without any aberrant, facial-nerve-lesion-induced sensory feedback. In each animal, M1 output was assessed in both hemispheres by mapping movements induced by intracortical microstimulation. M1 output was compared in different types of peripheral manipulations: (i) contralateral intact vibrissal pad (intact hemispheres), (ii) contralateral VII cut (VII hemispheres), (iii) contralateral ION cut (ION hemispheres), (iv) contralateral VII cut after contralateral ION cut (ION + VII hemispheres), (v) contralateral pad botulinum-toxin-injected after ION cut (ION + BTX hemispheres). Right and left hemispheres in untouched animals were the reference for normal M1 map (control hemispheres). Findings demonstrated that: (1) in ION hemispheres, the mean size of the vibrissae representation was not significantly different from those in intact and control hemispheres; (2) reorganization of the vibrissae movement representation clearly emerged only in hemispheres where the contralateral vibrissae pad had undergone motor output disconnection (VII cut hemispheres); (3) the persistent loss of vibrissae input did not change the M1 reorganization pattern during the first 48 h after motor paralysis (ION + VII cut and ION + BTX hemispheres). Thus, after motor paralysis, vibrissa input does not provide the gating signal necessary to trigger M1 reorganization.     

Receptive-field properties of rat ventral posterior medial neurons before and after selective kainic acid lesions of the trigeminal brain stem complex

Single neurons were recorded from the ventral posteromedial thalamic nucleus (VPM) of urethan-anesthetized rats. Six of these animals were intact, 28 sustained kainic acid (KA) lesions of trigeminal nucleus principalis (PrV), and 9 received similar lesions of trigeminal subnucleus interpolaris (SpVi). Four animals sustained PrV lesions that were followed, at an interval of 1-3 mo, by KA injections into SpVi. Special attention was paid to the receptive-field characteristics of neurons that were sensitive to deflection of the mystacial vibrissae. In normal animals, we recorded a total of 167 VPM neurons, 85% (n = 142) of which were vibrissa sensitive. The remaining VPM cells were excited by either guard hair deflection (8.4%), indentation of the skin (0.6%), or deflection of either vibrissae or guard hairs (1.8%). Seven cells (4.2%) were unresponsive. The topography of the trigeminal representation in VPM was similar to that reported previously by Waite (59). Vibrissa-sensitive neurons in intact rats generally gave rapidly adapting responses (84.5%), and only 16.2% were directionally selective. The vast majority (80.3%) of the vibrissa-sensitive cells were activated by deflection of only one whisker (1.2 +/- 0.5, mean +/- SD); none were excited by deflection of more than four vibrissae. Injections of KA into SpVi of otherwise intact rats (n = 9) had no appreciable effect on the receptive-field characteristics of vibrissa-sensitive VPM neurons. Injections of KA into PrV markedly altered the receptive-field properties of VPM cells. Recordings were made from 45 VPM neurons over a period extending from 0 to 10 h after KA injections into PrV in five rats. Of these cells, 4.4% were excited by vibrissa deflection and the remainder were unresponsive. Additional recordings from SpVi and the superior colliculus of these same animals indicated that the neurotoxin probably did not damage interpolaris neurons or their axons. Recordings were made from 394 VPM cells in 22 rats that survived 1-6 days after KA lesions of PrV. These experiments demonstrated an increase in the number of thalamic cells that were responsive to peripheral stimulation over this period. By 6 days after the lesion (4 animals), 52.8% of the 73 VPM neurons we recorded were excited by somatosensory stimuli. Of these, 89.5% were activated by deflection of one or more mystacial vibrissae. The average number of whiskers that excited a given VPM cell in these rats was 6.3 +/- 2.0 (SD). Recordings were made from VPM in five rats that survived 30-90 days after KA injections in PrV.(ABSTRACT TRUNCATED AT 400 WORDS)     

The vibrissal pad as a source of sensory information for the oculomotor system of the cat

Summary Responses from lateral rectus, medial rectus and retractor bulbi nerves were obtained following electrical stimulation of the vibrissal pad of the cat. Discharges in afferent fibres dissected from the infraorbital nerve were recorded during movements of the vibrissae and following electrical stimulation of the vibrissal pad. Both stimuli activated the same population of A fibers. Intracellular records were obtained from lateral rectus motoneurones identified antidromically in the principal abducens nucleus and from retractor bulbi motoneurones similarly identified in the accessory abducens nucleus. EPSPs (3 mV) were recorded in lateral rectus motoneurones following electrical stimulation of the ipsilateral vibrissal pad at a latency of 3.5 ms. Large-amplitude disynaptic EPSPs (15 mV) were recorded in retractor bulbi motoneurones following the same vibrissal stimulation. The synaptic excitation evoked in both lateral rectus and retractor bulbi motoneurones through stimulation of the ipsilateral vibrissal pad induced an early retraction followed by an abduction of the eye ball. The hypothesis is that the vibrissal message might complement other sensory modalities in the generation of patterned eye movements.Supported by CNRS (GR 45) and by Grant DGRST No. 78.7.3017     

Comparing vibrissal morphology and infraorbital foramen area in pinnipeds

Pinniped vibrissae are well-adapted to sensing in an aquatic environment, by being morphologically diverse and more sensitive than those of terrestrial species. However, it is both challenging and time-consuming to measure vibrissal sensitivity in many species. In terrestrial species, the infraorbital foramen (IOF) area is associated with vibrissal sensitivity and increases with vibrissal number. While pinnipeds are thought to have large IOF areas, this has not yet been systematically measured before. We investigated vibrissal morphology, IOF area, and skull size in 16 species of pinniped and 12 terrestrial Carnivora species. Pinnipeds had significantly larger skulls and IOF areas, longer vibrissae, and fewer vibrissae than the other Carnivora species. IOF area and vibrissal number were correlated in Pinnipeds, just as they are in terrestrial mammals. However, despite pinnipeds having significantly fewer vibrissae than other Carnivora species, their IOF area was not smaller, which might be due to pinnipeds having vibrissae that are innervated more. We propose that investigating normalized IOF area per vibrissa will offer an alternative way to approximate gross individual vibrissal sensitivity in pinnipeds and other mammalian species. Our data show that many species of pinniped, and some species of felids, are likely to have strongly innervated individual vibrissae, since they have high values of normalized IOF area per vibrissa. We suggest that species that hunt moving prey items in the dark will have more sensitive and specialized vibrissae, especially as they have to integrate between individual vibrissal signals to calculate the direction of moving prey during hunting.     

Denervation does not affect the growth of rat vibrissae

This study examines the hypothesis that neural factors influence the growth of rat vibrissae. We divided the vibrissae in rows alpha-delta, 1 and 2 and examined their regrowth during the first complete growth period in normal and nerve-lesioned rats. The lesions used were denervation through neonatal capsaicin treatment, surgical sympathecomy in adult rats, neurectomy of the mandibular and buccal branches of the facial nerve in adult rats or division of the infraorbital nerve in adult rats. Normal vibrissae developed a length of 51.1 mm and a diameter of 178 microm (row alpha-delta), 44.1 mm and 181 microm (row 1) and 33.2 mm and 165 microm (row 2). In all experimental groups the examined vibrissae developed a normal final length and proximal diameter. This indicates that local nerves do not influence vibrissal growth to any major extent.     

The role of perioral sensation in nipple attachment by weanling rat pups

Injecting .05 ml of 1% lidocaine into each vibrissal pad, or cutting the infraorbital nerves, abolished nipple attachment in weanling Wistar rat pups. Nipple attachment recovered following infraorbital section. Injecting the local anesthetic intraperitoneally, or into the region of the masseter muscles, did not disrupt attachment, indicating that the effect of the drug on suckling was specific to the site of injection and could not be attributed to systemic toxicity or paralysis of the masseter muscles. Performance on an olfactory-guided orientation task was not disrupted by lidocaine, indicating that the drug did not render pups anosmic. Tactile sensation in the vibrissal pads, rhinarium, and upper lip was abolished after injecting the drug into the vibrissal pads. Vibrissal movement was absent following injection of lidocaine into either the vibrissal pads or the region of the masseter muscles. Shaving the vibrissae did not disrupt nipple attachment. The results are interpreted as suggesting that the nipples' textural qualities elicit attachment in weanling pups.     

Reorganization of vibrissal motor representation following severing and repair of the facial nerve in adult rats

This study examined the ability of adult rat motor cortex to reorganize its relationship with the somatic musculature following the severing and regeneration of a motor nerve. For this purpose experiments were performed on ten male albino rats where the facial nerve on one side was severed, sutured and allowed to regenerate for 6 months. Cortical motor output organization was assessed by mapping the vibrissal movement area extension and thresholds evoked by intracortical electrical stimulation in anesthetized rats. In all ten animals, the cortical output pattern of the motor cortex contralateral to the normal side was compared with that contralateral to the reinnervated side. After facial nerve reinnervation, the most notable differences in primary motor cortex (M1) output organization in the hemispheres contralateral to the reinnervated side were: (a) the area from which vibrissa movements could be evoked at low thresholds was smaller (mean 1.2+/-0.38 mm, range 0.75-1.75 mm), decreasing to 64.2% below those in hemispheres contralateral to the normal side (mean 3.4+/-0.52 mm, range 2.5-4 mm). The reorganized vibrissa area consisted of contiguous or discontinuous points shrunken to the medialmost portion of normal M1 vibrissal representation. (b) There was a clear medial extension of the forelimb representation, and a more modest lateral expansion of eye representation, into the vibrissa territory. The mean threshold required to evoke vibrissa movements was significantly higher in the hemispheres contralateral to the reinnervated side than in the other hemispheres (normal 23.9+/-9.7 microA vs reinnervated 37.8+/-11.9 microA; P< or =0.0001; t-test). The stimulation currents required to evoke other types of body movements were similar in the normal and reinnervated sides. Similar results were observed in all rats. In conclusion, these results indicate that motor nerve reinnervation is sufficient to produce long-lasting changes at a higher motor cortical level. This supports the notion that central supranuclear mechanisms may also be involved in the disorder of facial movements observed after facial nerve reinnervation.     

Changes in the central projection pattern of vibrissae innervating primary sensory neurons after peripheral nerve injury in the rat

The central representation of a normal vibrissa nerve and the corresponding nerve after transection and regeneration of the infraorbital nerve has been studied by the use of transganglionic transport of horseradish peroxidase in the adult rat. The normal vibrissa nerve terminated in a well-defined area within nucleus caudalis and C1 dorsal horn. In contrast, the regenerated vibrissa nerve showed a widespread central termination pattern indicating a pronounced loss of somatotopic organization. These changes in somatotopic organization could contribute to an inability to correctly localize a sensory stimulus; this is a common clinical finding after peripheral nerve injury and regeneration.     

Uptake and retrograde axonal transport of horseradish peroxidase in regenerating facial motor neurons of the mouse

Summary Uptake and retrograde axonal transport of intravenously injected horseradish peroxidase (HRP) was studied during regeneration after a crush injury of the facial nerve of the mouse. The circulation time of HRP was 12 to 24 h. HRP injected immediately after the crush diffused into injured axons in the crushed region and accumulated subsequently in perikarya of facial neurons in the brain stem. After a time interval of 1 h or 5 days between the crush and the injection only a faint HRP accumulation occurred in a few facial neurons. After an interval of 7 days a moderate number of neurons had incorporated the tracer, while after more than 9 days the HRP activity in the regenerating neurons was more pronounced than in the contralateral neurons. Ultrastructurally, muscles of the vibrissae showed denervated subneural apparatuses 6 days after the crush. 8 days after the crush regenerating axon terminals containing small clusters of synaptic vesicles, dense cored vesicles and some HRP-labelled vesicles, were found over some gutters and after 10 to 13 days all examined gutters contained axon terminals with large numbers of synaptic vesicles and some HRP-containing vesicles. More than one axon terminal profile was seen in the same synaptic gutter. 32 and 64 days after the crush the neuromuscular junctions had regained a more mature appearance. The calibre spectra of the crushed facial nerves still showed a shift towards smaller diameters 134 days after the crush, at a time when a slight increase in HRP activity in the facial neurons persisted.     

Survival and regeneration of cutaneous and muscular afferent neurons after peripheral nerve injury in adult rats

Peripheral nerve injury induces the retrograde degeneration of dorsal root ganglion (DRG) cells, which affects predominantly the small-diameter cutaneous afferent neurons. This study compares the time-course of retrograde cell death in cutaneous and muscular DRG cells after peripheral nerve transection as well as neuronal survival and axonal regeneration after primary repair or nerve grafting. For comparison, spinal motoneurons were also included in the study. Sural and medial gastrocnemius DRG neurons were retrogradely labeled with the fluorescent tracers Fast Blue (FB) or Fluoro-Gold (FG) from the homonymous transected nerves. Survival of labeled sural and gastrocnemius DRG cells was assessed at 3 days and 1–24 weeks after axotomy. To evaluate axonal regeneration, the sciatic nerve was transected proximally at 1 week after FB-labeling of the sural and medial gastrocnemius nerves and immediately reconstructed using primary repair or autologous nerve grafting. Twelve weeks later, the fluorescent tracer Fluoro-Ruby (FR) was applied 10 mm distal to the sciatic lesion in order to double-label sural and gastrocnemius neurons that had regenerated across the repair site. Counts of labeled gastrocnemius DRG neurons did not reveal any significant retrograde cell death after nerve transection. In contrast, sural axotomy induced a delayed loss of sural DRG cells, which amounted to 22% at 4 weeks and 43–48% at 8–24 weeks postoperatively. Proximal transection of the sciatic nerve at 1 week after injury to the sural or gastrocnemius nerves neither further increased retrograde DRG degeneration, nor did it affect survival of sural or gastrocnemius motoneurons. Primary repair or peripheral nerve grafting supported regeneration of 53–60% of the spinal motoneurons and 47–49% of the muscular DRG neurons at 13 weeks postoperatively. In the cutaneous DRG neurons, primary repair or peripheral nerve grafting increased survival by 19–30% and promoted regeneration of 46–66% of the cells. The present results suggest that cutaneous DRG neurons are more sensitive to peripheral nerve injury than muscular DRG cells, but that their regenerative capacity does not differ from that of the latter cells. However, the retrograde loss of cutaneous DRG cells taking place despite immediate nerve repair would still limit the recovery of cutaneous sensory functions.     

Ginsenoside Rg1 promotes peripheral nerve regeneration in rat model of nerve crush injury

Searching for effective drugs which are capable of promoting nerve regeneration after nerve injuries has gained extensive attention. Ginsenoside Rg1 (GRg1) is one of the bioactive compounds extracted from ginseng. GRg1 has been shown to be neuroprotective in many in vitro studies, which raises the possibility of using GRg1 as a neuroprotective agent after nerve injuries. However, such a possibility has never been tested in in vivo studies. The present study was designed to investigate the efficacy of GRg1 in promoting nerve regeneration after nerve crush injury in rats. All rats were randomly divided into four groups (n = 8 in each group) after crush injury and were intraperitoneally administrated daily for 4 weeks with 1 mg/kg, or 5 mg/kg GRg1 (low or high dose GRg1 groups), or 100 μg/kg mecobalamin or normal saline, respectively. The axonal regeneration was investigated by retrograde labeling and morphometric analysis. The motor functional recovery was evaluated by electrophysiological studies, behavioral tests and histological appearance of the target muscles. Our data showed that high dose GRg1 achieved better axonal regeneration and functional recovery than those achieved by low dose GRg1 and mecobalamin. The final outcome of low dose GRg1 and mecobalamin was similar in both morphological and functional items, which was significantly better than that in saline group. These findings show that GRg1 is capable of promoting nerve regeneration after nerve injuries, suggesting the possibility of developing GRg1 a neuroprotective drug for peripheral nerve repair applications.     

Experience-dependent changes in function and anatomy of adult barrel cortex

Manipulations of sensory input to vibrissal mechanoreceptors can modify columnar functioning of the barrel cortex in adult animals. In mice, partial vibrissectomy sparing one row of vibrissae in young adults results 7 days later in an increase in the functional cortical column activated by the spared whiskers and visualized with 2-deoxyglucose autoradiography. The increase in the extent of the labelled area is visible in all cortical layers, but particularly in layer V, where the metabolic labelling is more intense in the representation of the spared vibrissae. Two months after vibrissectomy the enlargement of the labelled area is accentuated. Deprivation of a row of vibrissae results in a decrease in the areal extent of its cortical representation. Investigations of cortico-cortical connections carried out in living slices of the barrel cortex of mice 2 months after vibrissectomy sparing one row of whiskers, revealed elongation and increased branching of axons originating in the spared cortical column. The dendritic spine density was increased on the basal dendrites of layer V pyramidal neurons of the spared column and decreased on layer III apical dendrites of the deprived column. Thus, prolonged changes in functional activation of adult barrel cortex are accompanied by rearrangement of cortico-cortical circuitry.     

Tactile impoverishment and sensorimotor restriction deteriorate the forepaw cutaneous map in the primary somatosensory cortex of adult rats

We investigated the effects of sensory deprivation on the forepaw representation in the primary somatosensory cortex (SI) in the adult rat. Cortical maps were constructed from high-resolution multiunit recordings of the response of layer IV neurons to somatosensory stimuli. The main features of the forepaw representation were described in terms of areal extent and topography of the cortical map, and sensory submodality, size, and location of the receptive field (RF) of small clusters of the cortical neurons. After being weaned, two groups of Long-Evans rats were housed in a standard (SE) or impoverished (IE) environment for 65–115 days. A third group of SE rats was subjected to severe sensorimotor restriction (SR) of one forepaw for 7 days or 14 days, by using a one-sleeved cast. A concomitant effect of unilateral forelimb immobilization was a forced use of the nonrestricted forelimb in postural balance. The maps of both forepaws were derived 24 h after the cast was removed and the animal was allowed normal limb use. In a fourth group, SE rats experienced a 7-day immobilization followed by symmetrical limb use for 7 days before we mapped the hemisphere contralateral to the casted limb. For the SE and IE rats, the total areal extent of the cutaneous forepaw representation was similar, but IE rats exhibited a significant expansion of cortical islets serving high-threshold, presumably noncutaneous inputs, which were included in the cutaneous maps. In addition, SI neurons of IE rats had greatly enlarged glabrous, but not hairy, skin RFs. For the SR rats, the areal extent of the cutaneous map of the casted forepaw decreased by about 50%, after both 7- and 14-day forelimb immobilization. Large cortical sectors presumed to be formerly activated by cutaneous inputs were driven by high-threshold inputs that disrupted the somatotopic representation of the forepaw skin surfaces. These ”emergent” representational sectors were topographically organized. By contrast, the areal extent and topography of the noncasted forepaw representation did not differ from those of SE rats. The size of glabrous RFs on the casted forepaw was similar to that of SE rats. On the contrary, glabrous RFs on the noncasted forepaw of SR rats were larger than those on their casted forepaw. The size of hairy RFs was not altered by the forelimb restriction. Interestingly, alteration of the somatotopic features of the casted forepaw map persisted after 7 days of symmetric use of the forelimbs. The present study demonstrates that continuous sensory experience is needed for the organizational features of SI maps to be maintained. Received: 22 February 1999 / Accepted: 8 July 1999     

EphA4 is necessary for spatially selective peripheral somatosensory topography

Somatosensation is the primary sensory modality employed by rodents in navigating their environments, and mystacial vibrissae on the snout are the primary conveyors of this information to the murine brain. The layout of vibrissae is spatially stereotyped and topographic connections faithfully maintain this layout throughout the neuraxis. Several factors have been shown to influence general vibrissal innervation by trigeminal neurons. Here, the role of a cell surface receptor, EphA4, in directing position‐dependent vibrissal innervation is examined. EphA4 is expressed in the ventral region of the presumptive whisker pad and EphA4^?/? mice lack the ventroposterior‐most vibrissae. Analyses reveal that ventral trigeminal axons are abnormal, failing to innervate emerging vibrissae, and resulting in the absence of a select group of vibrissae in EphA4^?/? mice. EphA4's selective effect on a subset of whiskers implicates cell‐based signaling in the establishment of position‐dependent connectivity and topography in the peripheral somatosensory system. Developmental Dynamics 239:630–638, 2010. © 2009 Wiley‐Liss, Inc.     

Regeneration in theXenopus tadpole optic nerve is preceded by a massive macrophage/microglial response

Summary Changes in the optic nerve following a crush lesion and during axonal regeneration have been studied inXenopus tadpoles, using ultrastructural and immunohistological methods. Degeneration of both unmyelinated and myelinated axons is very rapid and leads to the formation, within 5 days, of a nerve which consists largely of degeneration debris and cells. Immunohistological analysis with monoclonal antibody 5F4 shows that there is a rapid and extensive microglial/macrophage response to crush of the nerve. Regenerating axons have begun to enter the distal stump by 5 days and grow along the outer part of the nerve in close approximation to the astrocytic glia limitans. Between 5 and 10 days after nerve crush, regenerating axons reach and pass the chiasma. Macrophages are seen in the nerve at the site of the lesion within 1 h, and the response peaks between 3–5 days, just before axonal regeneration gets under way.     

Anatomical correlates of representational map reorganization induced by partial vibrissectomy in the barrel cortex of adult mice.

We examined the potential for changes in cortical connectivity to accompany long-term plastic changes in functional cortical representations of mystacial vibrissae. Plasticity in the barrel cortex of young adult mice was evoked by vibrissectomy that spared row C of whiskers. We found that 2-deoxyglucose brain mapping causes a progressive expansion of cortical representation of the spared vibrissae. Two months after vibrissectomy, when the width of the cortical map of the spared row of vibrissae doubled, living cortical slices of the barrel cortex were injected with fluorescent dextrans. The injections were centered on spared, deprived and control vibrissal columns. The injections labeled three intracortical projection systems: (i) local connections from one vibrissal column to neighboring columns; (ii) long-range projections running in the septa and walls of the barrels and spanning several barrels; and (iii) very-long-range fibers running horizontally in the lower part of layer V. The local, short-range projection system was analysed following small injections into the centers of columns in layers III and IV. We found that injections into spared barrels labeled axons extending for significantly greater distances in all layers (except layer V), and labeled cell bodies situated significantly further, than after injections into deprived or control barrels. Also, the total axonal density labeled by injections into the spared barrel was higher by 70% than for the deprived or control barrels. Alterations of topographical maps in adult somatosensory cortex may occur immediately after functional denervation, but may also increase with time, as in the case of our experimental situation. Our results indicate that persistent, long-term plastic change can remodel connectivity in the barrel cortex.     

Effects of different types of injury to the inferior alveolar nerve on the behavior of Schwann cells during the regeneration of periodontal nerve fibers of rat incisor

The present study reports on different regeneration patterns of axons and Schwann cells in the periodontal ligament of the rat incisor using immunohistochemistry of protein gene product 9.5 (PGP 9.5) and S-100 protein. Three kinds of injury (transection, crush and segmental resection) were applied to the inferior alveolar nerve. In normal animals, PGP 9.5- and S-100-immunoreactivities were detected in the axons and Schwann cell elements of periodontal Ruffini endings, respectively. They were restricted to the alveolus-related part, occurring only rarely in the tooth-related part and in the shear zone (the border between the alveolus-related and tooth-related parts). Both transection and segmental resection caused the complete disappearance of PGP 9.5-immunoreactive nerve fibers in the periodontal ligament, while a small number of them could be found following the crush injury. Regenerating PGP 9.5-reactive nerve fibers appeared at 5 days and 21 days following the transection and segmental resection, respectively. The regeneration of periodontal nerve fibers completed in a period of 21-28 days and 14-21 days following the transection and crush, respectively, but was not completed even at 56 days following the segmental resection. The behavior of Schwann cells during regeneration was similar after the different nerve injuries; spindle-shaped S-100-immunoreactive cells, presumably Schwann cells, appeared in the shear zone and the tooth-related part. These cells disappeared 5-7 days prior to the completion of the regeneration of axonal elements of the periodontal ligament following the transection and crush. Following the segmental resection, in contrast, spindle-shaped S-100-positive cells disappeared from the tooth-related part at 42 days, although the axonal regeneration of periodontal Ruffini endings proceeded even until 56 days. We thus conclude that the duration of the migration of Schwann cells depends on the state of the regeneration of axons.     

Environmental factors contribute to the enhanced regeneration of frog sciatic sensory axons by a conditioning lesion

The outgrowth of regenerating frog sciatic sensory axons after a crush lesion was measured from the distribution of axonally transported radioactive proteins. Five days after a single test crush the regeneration distance was 3.6 +/- 0.3 mm. If the nerve was subjected to a conditioning lesion 15 mm distal to and 5, 10 or 17 days prior to the test crush, there was an increased outgrowth distance (5.1 +/- 0.2 mm) 5 days after the test crush when the conditioning interval was 10 days. Prolongation of the time interval between the two lesions to 17 days did not significantly change the enhanced outgrowth. In contrast, if the conditioning and test lesions were applied at the same site, the regeneration distance 5 days after the test crush was already significantly increased after a conditioning interval of 5 days (5.9 +/- 0.5 mm). It was further enhanced after an interval of 10 days (7.8 +/- 0.5 mm) and yet further after 17 days (9.2 +/- 0.5 mm). When the conditioning and test lesions were superimposed, the regeneration occurred through a region of the nerve that was pre-degenerated due to the conditioning lesion. The positive correlation between the degree of degeneration and the outgrowth distance supports the theory that environmental factors contribute to the regenerating ability of peripheral nerves.