Deafferented Side Research Articles

Lateralized Supraspinal Functional Connectivity Correlate with Pain and Motor Dysfunction in Rat Hemicontusion Cervical Spinal Cord Injury.

Afferent nociceptive activity in the reorganizing spinal cord after SCI influences supraspinal regions to establish pain. Clinical evidence of poor motor functional recovery in SCI patients with pain, led us to hypothesize that sensory-motor integration transforms into sensory-motor interference to manifest pain. This was tested by investigating supraspinal changes in a rat model of hemicontusion cervical SCI. Animals displayed ipsilateral forelimb motor dysfunction and pain, which persisted at 6 weeks after SCI. Using resting state fMRI at 8 weeks after SCI, RSFC across 14 ROIs involved in nociception, indicated lateral differences with a relatively weaker right-right connectivity (deafferented-contralateral) compared to left-left (unaffected-ipsilateral). However, the sensory (S1) and motor (M1/M2) networks showed greater RSFC using right hemisphere ROI seeds when compared to left. Voxel seeds from the somatosensory forelimb (S1FL) and M1/M2 representations reproduced the SCI-induced sensory and motor RSFC enhancements observed using the ROI seeds. Larger local connectivity occurred in the right sensory and motor networks amidst a decreasing overall local connectivity. This maladaptive reorganization of the right (deafferented) hemisphere localized the sensory component of pain emerging from the ipsilateral forepaw. A significant expansion of the sensory and motor network s overlap occurred globally after SCI when compared to sham, supporting the hypothesis that sensory and motor interference manifests pain. Voxel-seed based analysis revealed greater sensory and motor network overlap in the left hemisphere when compared to the right. This left predominance of the overlap suggested relatively larger pain processing in the unaffected hemisphere, when compared to the deafferented side.

Multiple Morphometric Assessment of Microglial Cells in Deafferented Spinal Trigeminal Nucleus.

Microglia (MG) are the first cells to react to the abnormal incoming signals that follow an injury of sensory nerves and play a critical role in the development and maintenance of neuropathic pain, a common sequel of nerve injuries. Here we present population data on cell number, soma size, and length of processes of MG in the caudal division of the spinal trigeminal nucleus (Sp5C) in control mice and at the peak of microgliosis (7 days) following unilateral transection of the infraorbital nerve (IoN). The study is performed combining several bias- and assumption-free imaging and stereological approaches with different immunolabeling procedures, with the objective of tackling some hard problems that often hinder proper execution of MG morphometric studies. Our approach may easily be applied to low-density MG populations, but also works, with limited biases, in territories where MG cell bodies and processes form dense meshworks. In controls, and contralaterally to the deafferented side, MG cell body size and shape and branching pattern matched well the descriptions of “resting” or “surveillant” MG described elsewhere, with only moderate intersubject variability. On the superficial laminae of the deafferented side, however, MG displayed on average larger somata and remarkable diversity in shape. The number of cells and the length of MG processes per mm3 increased 5 and 2.5 times, respectively, indicating a net 50% decrease in the mean length of processes per cell. By using specific immunolabeling and cell sorting of vascular macrophages, we found only a negligible fraction of these cells in Sp5C, with no differences between controls and deafferented animals, suggesting that blood-borne monocytes play at most a very limited role in the microgliosis occurring following sensory nerve deafferentation. In sum, here we present reliable morphometric data on MG in control and deafferented trigeminal nuclei using efficient methods that we propose may equally be applied to any morphometric population analysis of these cells under different physiological or pathological conditions.

Neurophysiological Effects of Dorsal Root Ganglion Stimulation (DRGS) in Pain Processing at the Cortical Level

Dorsal root ganglion stimulation (DRGS) has been used successfully against localized neuropathic pain. Nevertheless, the effects of DRGS on pain processing, particularly at the cortical level, remain largely unknown. In this study, we investigated whether positive responses to DRGS treatment would alter patients' laser-evoked potentials (LEP). We prospectively enrolled 12 adult patients with unilateral localized neuropathic pain in the lower limbs or inguinal region and followed them up for six months. LEPs were assessed at baseline, after one month of DRGS, and after six months of DRGS. Clinical assessment included the Numerical Rating Scale (NRS), Brief Pain Inventory (BPI), SF-36, and Beck Depression Inventory (BDI). For each patient, LEP amplitudes and latencies of the N2 and P2 components on the deafferented side were measured and compared to those of the healthy side and correlated with pain intensity, as measured with the NRS. At the one- and six-month follow-ups, N2-P2 amplitudes were significantly greater and NRS scores were significantly lower compared with baseline (all p's < 0.01). There was a negative correlation between LEP amplitudes and NRS scores (rs = -0.31, p < 0.10). DRGS is able to restore LEPs to normal values in patients with localized neuropathic pain, and LEP alterations are correlated with clinical response in terms of pain intensity.

The dynamic expression of Mash1 in the hippocampal subgranular zone after fimbria-fornix transection

Mash1, a member of the basic helix-loop-helix (bHLH) transcription factor family, has previously been considered essential for neuronal differentiation and specification in the nervous system. In this study, we investigated the expression of Mash1 in the hippocampus after fimbria-fornix (FF) transection. Western blot showed that protein of Mash1 increased significantly and peaked at day 7 after FF transection. Immunofluorescence indicated that after FF transection, more newborn cells differentiated into Mash1 positive cells in the deafferented side than that in the normal side, and we investigated that in the neurogenic area, subgranular zone (SGZ), a part of Mash1 positive cells were NeuN positive, and more Mash1/NeuN double positive neurons were identified in the deafferented side than that in the normal side. Additionally, the number of Mash1/NeuN double positive neurons in SGZ increased significantly and peaked at day 7 after FF transection. In vitro, immunofluorescence revealed that extracts of the deafferented hippocampus promoted neuronal differentiation to a greater extent than extracts from normal hippocampus. Deafferented extracts also enhanced Mash1 expression in MAP-2 positive neurons. This study concludes that after FF transection, Mash1 expression in the deafferented hippocampus increased and might play an important role in inducing local progenitors to differentiate into neurons.

Brn‐4 is upregulated in the deafferented hippocampus and promotes neuronal differentiation of neural progenitors in vitro

Fimbria-fornix (FF), the septo-hippocampal pathway, was transected to model Alzheimer's disease (AD), which is characterized by loss of cholinergic afferent fibers in hippocampus. Various alternations may happen in the deafferented hippocampus. In this study, we determined the expression of Brn-4 in hippocampus after FF lesion. RT-PCR and Western blot showed that mRNA transcription and protein of Brn-4 increased significantly and reached to the peak at day 14 after FF lesion. Hybridization and immunohistochemistry indicated that Brn-4 signals in hippocampus and dentate gyrus (DG) of the deafferented side were significantly stronger than the normal side. More Brn-4 positive cells were identified in the DG of deafferented hippocampus. In the pyramidal and granular cells, Brn-4 positive cells were all NeuN positive neurons, whereas in the neurogenic area, subgranular zone (SGZ), only a part of Brn-4 positive cells were NeuN positive, and these Brn-4/NeuN double positive neurons in SGZ and hilus of DG increased significantly after the trauma induced by FF lesion. In vitro Brn-4 antibody attenuated the role of extract from deafferented hippocampus in promoting differentiation of hippocampal progenitors into MAP-2 positive neurons. This study demonstrated that after FF lesion, Brn-4 in the deafferented hippocampus was upregulated and might play an important role in inducing local progenitors to differentiate into neurons, which may compensate for the loss of cholinergic afferent fibers or other dysfunctions.

Facilitation of Stepping with Epidural Stimulation in Spinal Rats: Role of Sensory Input

We investigated the role of afferent information during recovery of coordinated rhythmic activity of the hindlimbs in rats with a complete spinal cord section (approximately T8) and unilateral deafferentation (T12-S2) to answer the following questions: (1) Can bilateral stepping be generated with only afferent projections intact on one side? (2) Can the sensory input from the non-deafferented side compensate for the loss of the afferent input from the deafferented side through the crossed connections within the lumbosacral spinal cord? (3) Which afferent projections to the spinal cord from the non-deafferented side predominantly mediate the effect of epidural stimulation to facilitate stepping? Recovery of stepping ability was tested under the facilitating influence of epidural stimulation at the S1 spinal segment, or epidural stimulation plus quipazine, a 5-HT agonist. All chronic spinal rats were able to generate stepping-like patterns on a moving treadmill on the non-deafferented, but not deafferented, side from 3 to 7 weeks after surgery when facilitated by epidural stimulation. Adaptation to the loss of unilateral afferent input was evident at 7 weeks after surgery, when some movements occurred on the deafferented side. Spinal-cord-evoked potentials were observed on both sides, although middle (monosynaptic) and late (long latency) responses were more prominent on the non-deafferented side. The afferent information arising from the non-deafferented side, however, eventually could mediate limited restoration of hindlimb movements on the deafferented side. These data suggest that facilitation of stepping with epidural stimulation is mediated primarily through ipsilateral afferents that project to the locomotor networks.

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

L1 is a cell adhesion molecule associated with axonal outgrowth and fasciculation during spinal cord development and may reiterate its developmental role in adults following injury; L1 is upregulated on certain sprouting and regenerating axons in adults, but it is unclear if L1 expression is necessary for, or contributes to, regrowth of axons. This study asks if L1 is required for small-diameter primary afferents to sprout by conducting unilateral dorsal rhizotomies (six segments; T10–L2) on both wild-type and L1 mutant mice. First we determined that L1 co-localizes substantially with the peptidergic (calcitonin gene-related peptide; CGRP) but minimally with the nonpeptidergic (isolectin B4; IB4) primary afferents in intact wild-type and L1 mutant mice. However, we encountered a complication using IB4 to identify primary afferents post-rhizotomy; we detected extensive abnormal IB4 expression in the dorsal horn and dorsal columns. Much of this aberrant IB4 labeling is associated with fibrous astrocytes and microglia. Five days after dorsal rhizotomy a large decrease in peptidergic and nonpeptidergic afferents is evident on the deafferented side in both wild-type and L1 mutants. Three months after surgery the peptidergic primary afferents sprouted into the center of the denervated dorsal horn in both wild-type and mutant mice, and quantitative analyses confirmed a sprouting density of similar magnitude in both genotypes. In contrast, we did not detect sprouting in the nonpeptidergic primary afferents in either genotype. These results suggest that the absence of L1 neither diminishes nor enhances sprouting of peptidergic small-diameter primary afferent axons following a dorsal rhizotomy.

Deafferentation induces novel axonal projections in the auditory brainstem after hearing onset

Deafferentation of neural tissue can result in cell death, morphological changes, and/or alterations in sources of innervation. These changes often occur during a limited period of development. In the auditory brainstem, the ventral cochlear nucleus (VCN) projects to the contralateral but not ipsilateral medial nucleus of the trapezoid body (MNTB). This pathway is part of a circuit that computes interaural intensity differences used in sound localization. Previous studies have shown that, after the cochlea is removed early in postnatal development, cells in the VCN on the deafferented side die, and the intact VCN innervates MNTB on both sides of the brain. These changes after cochlea removal are limited to an early postnatal period that preceeds hearing onset. In this study, we lesioned the VCN directly to evaluate plasticity in axonal pathways after hearing onset. We found that novel projections from the intact VCN to ipsilateral MNTB emerge after lesions performed as late as postnatal day 25. The morphological sequence of events is similar to that seen during the initial development of this pathway. These data suggest that plasticity in the auditory brainstem is possible when pathways are challenged with denervation of target nuclei. The results show that the opportunity for plasticity in auditory brainstem circuitry is more prolonged than previously thought and that novel pathways can form after the normal pathways are fully mature and functional. Moreover, sensitive periods for changes in individual pathways are independently regulated.

Development of rodent whisking: Trigeminal input and central pattern generation

To examine the contribution of whisker inputs to the initial emergence and subsequent refinement of the rodent whisking pattern we combined surgical treatments producing varying degrees of postnatal whisker deafferentation with observations and video analysis of whisking across the first month of life. Whisking emerges during the second postnatal week, preceding eye opening by a few days. In contrast to the absence of deafferentation effects in adults, whisker deafferentation in pups, if carried out between the second and third postnatal week, delays (but does not prevent) the emergence of whisker movements and disrupts the development of normal whisking kinematics and coordination. The extent of the delay varies directly with the reduction in whisker input. When regeneration of the nerve is prevented by a cyanoacrylate block emergence of the normal pattern may be delayed indefinitely. Moreover, section of the whisker motor nerve contralateral to the deafferented side, substantially potentiates the effects of the initial deafferentation. These results confirm and extend an earlier description of the development of whisking in normal rat pups (Welker, Behaviour 12:223–244, ), fix the time of its initial emergence more precisely at P (postnatal day) 11–13, and suggest a critical role for trigeminal afference in the development of the normal whisking pattern. They are discussed in relation to the development of pattern generating mechanisms in the rodent whisker system.

L1 CAM expression in the superficial dorsal horn is derived from the dorsal root ganglion

The cell adhesion molecule L1 is highly expressed on embryonic axons and may play a role in axonal outgrowth and fasciculation. Generally only low levels of L1 are found in adult spinal cord except for intense labeling in Lissauer's tract, in laminae I-II, and on dorsolateral funicular axons. In this study we determine the source of L1 immunoreactivity in the dorsal spinal cord, the presence of L1 expression on sprouting axons, and the effect of exercise on L1 expression. We determined the source of L1 immunoreactivity in the superficial dorsal horn by performing acute unilateral rhizotomies (T12-L4) in adult rats. This resulted in a marked decrease in L1 expression in Lissauer's tract and laminae I-II on the deafferented side. The peptidergic and nonpeptidergic small-diameter primary afferent markers, calcitonin gene-related peptide (CGRP) and the lectin IB4 respectively, closely correlated with L1 expression and also decreased dramatically after rhizotomy. Considering its developmental role, we asked whether L1 was expressed on sprouting axons following chronic rhizotomy. L1 and CGRP, but not IB4, were detected on sprouting axons. Lastly, we investigated the effect of exercise on L1 expression by giving animals with chronic rhizotomies free access to an exercise wheel. After extensive exercise, L1, CGRP, and IB4 expression levels were unchanged compared with those of sedentary chronic animals. Combined, these data demonstrate that the dorsal root ganglia is a major source of L1-positive axons in the superficial dorsal horn, that both L1 and CGRP identify sprouting axons following rhizotomy, and that exercise does not upregulate L1 expression.

Long-Term Plasticity of Ipsilesional Medial Vestibular Nucleus Neurons After Unilateral Labyrinthectomy

Unilateral labyrinthectomy results in oculomotor and postural disturbances that regress in a few days during vestibular compensation. The long-term (after 1 mo) consequences of unilateral labyrinthectomy were investigated by characterizing the static and dynamic membrane properties of the ipsilesional vestibular neurons recorded intracellularly in guinea pig brain stem slices. We compared the responses of type A and type B medial vestibular nucleus neurons identified in vitro to current steps and ramps and to sinusoidal currents of various frequencies. All ipsilesional vestibular neurons were depolarized by 6-10 mV at rest compared with the cells recorded from control slices. Both their average membrane potential and firing threshold were more depolarized, which suggests that changes in active conductances compensated for the loss of excitatory afferents. The afterhyperpolarization and discharge regularity of type B but not type A neurons were increased. All ipsilesional vestibular cells became more sensitive to current injections over a large range of frequencies (0.2-30 Hz), but this increase in sensitivity was greater for type B than for type A neurons. This was associated with an increase of the peak frequency of linear response restricted to type B neurons, from 4-6 to 12-14 Hz. Altogether, we show that long-term vestibular compensation involves major changes in the membrane properties of vestibular neurons on the deafferented side. Many of the static and dynamic membrane properties of type B neurons became more similar to those of type A neurons than in control slices, leading to an increase in the overall homogeneity of medial vestibular nucleus neurons.

Microglia, Astrocytes, and Macrophages React Differentially to Central and Peripheral Lesions in the Developing and Mature Rat Whisker-to-Barrel Pathway: A Study Using Immunohistochemistry for Lipocortin1, Phosphotyrosine, S100β, and Mannose Receptors

Adult and neonatal rats were subjected to transection of the left infraorbital nerve or ablation of the left parietal cortex. The ensuing glial reaction in the whisker-to-barrel pathway was studied with immunohistochemistry for Lipocortin1- (LC1+), phosphotyrosine- (PY+), S100β- (S100β+), and mannose receptor- (MR+) immunoreactive microglia, astrocytes, and macrophages. Four days after infraorbital nerve transection in adult rats, LC1+ and PY+ microglia were prominently increased in the trigeminal sensory brain-stem nuclei on the deafferented side compared with the intact side. Changes were negligible at the second synapse of the pathway, i.e., the thalamic ventroposterior medial nucleus. Cortical ablation in adults led to an increase in microglia in the ipsilateral ventroposterior medial nucleus that reciprocally connects with the ablated cortex. Moreover, microglial reactions occurred in the contralateral trigeminal sensory brain-stem nuclei in which corticofugal projections from the ablated cortex terminate. S100β+ astrocytes, in contrast, appeared unaltered after both types of lesion in adults. In neonates, LC1+, PY+, and S100β+ cells did not have the adult morphology of microglia or astrocytes. Four days after nerve transection, LC1+ and PY+ cells were sparse and remained unchanged. In contrast, S100β+ cells substantially increased in the deafferented trigeminal brain-stem nuclei. Four days after cortical ablation in neonates, LC1+, PY+, and S100β+ cells had accumulated in the deprived thalamus. In contrast to adults, many of these cells were MR+ macrophages. In the deprived brain-stem, only S100β+ cells increased and none were macrophages. Therefore, macrophages do not appear to stem from microglia, and neonatal LC1+, PY+, and S100β+ cells may possess functions different from those in adults.

Metabolic changes in the nucleus of the optic tract after monocular enucleation as revealed by cytochrome oxidase histochemistry.

The histochemistry for the mitochondrial enzyme cytochrome oxidase (CO) was used to evaluate the levels of metabolic activity in neurons of the nucleus of the optic tract (NOT) and dorsal terminal nucleus (DTN) in the opossum (Didelphis aurita). The observations were performed in four groups: normal juveniles (4 months old), monocularly enucleated juveniles analysed when adults, normal adults (8 to 18 months old) and monocularly enucleated adults. CO labeled cells were observed to have a similar distribution along the NOT-DTN anteroposterior axis in both juvenile and adult normal animals. Monocular enucleation performed in adults produced a significant reduction of the reactive neuropil but not of the number of CO labeled cells in the deafferented NOT-DTN: the number of labeled neurons per section in the deafferented side matched those of the ipsilateral complex. In juveniles, however, this procedure caused a systematic reduction of the number of CO labeled cells in the contralateral NOT-DTN in comparison to the spared complex. The lack of reduction in the number of neurons found on the deafferented side of the NOT-DTN of monocularly enucleated adult opossums compared with the ipsilateral side might result from the presence of compensatory inputs to maintain their metabolic equivalence. However, when the monocular enucleation was performed in juvenile opossums, a statistically significant asymmetry of CO neurons in the NOT-DTN was observed. In other words, the compensatory mechanisms proposed for the adults were either absent or insufficient to achieve symmetry in juveniles, suggesting a more heavily reliance in the retinal input.

Chronic inhibition of NOS does not prevent plasticity of rat somatosensory (S1) cortex following deafferentation

Nitric oxide (NO) has been proposed as an intercellular messenger mediating postsynaptic to presynaptic information transfer in the induction of long-term potentiation. A number of studies support the possible involvement of NO in synaptic plasticity. NO may have a role in synaptogenesis and synaptic plasticity in developing rat brain and may play a fundamental part in the process of regeneration, plasticity, and retargeting of axons following injury. We examined the possible role of NO on plasticity in the rat first somatosensory cortex with [ 14 C ]2-deoxyglucose (2-DG) autoradiography in rats treated daily with l-nitroarginine ( l-NA) following neonatal unilateral vibrissae deafferentation. After 6 weeks of l-NA treatment, the local cerebral glucose utilization (LCGU) and the spatial extent of the metabolic activation following stimulation of the spared whisker was measured. NOS catalytic activity exhibited significant inhibition throughout the treatment period. Vibrissae deafferentation produced a small but not statistically significant increase of LCGU in the vibrissa activated C3 barrel, and l-NA treatment did not alter the activation of LCGU in the deafferented cortex following whisker stimulation. Additionally, l-NA treatment did not alter the area of metabolic activation on either the non-deafferented side or the deafferented side. Deafferentation produced a 298% increase in the metabolic representation of the spared C3 barrel following stimulation in the saline treated animals, a 257% increase in the chronically l-NA treated animals, and a 256% increase in the short-term treated animals, all with respect to the response in the non-deafferented cortex. Metabolic plasticity in the barrel cortex was not attenuated by l-NA treatment. These results show that nitric oxide does not play a major role on developmental cortical plasticity induced by vibrissae deafferentation in the rat.

Human horizontal vestibulo-ocular reflex initiation: effects of acceleration, target distance, and unilateral deafferentation.

The vestibulo-ocular reflex (VOR) generates compensatory eye movements in response to angular and linear acceleration sensed by semicircular canals and otoliths respectively. Gaze stabilization demands that responses to linear acceleration be adjusted for viewing distance. This study in humans determined the transient dynamics of VOR initiation during angular and linear acceleration, modification of the VOR by viewing distance, and the effect of unilateral deafferentation. Combinations of unpredictable transient angular and linear head rotation were created by whole body yaw rotation about eccentric axes: 10 cm anterior to eyes, centered between eyes, centered between otoliths, and 20 cm posterior to eyes. Subjects viewed a target 500, 30, or 15 cm away that was extinguished immediately before rotation. There were four stimulus intensities up to a maximum peak acceleration of 2,800 degrees/s2. The normal initial VOR response began 7-10 ms after onset of head rotation. Response gain (eye velocity/head velocity) for near as compared with distant targets was increased as early as 1-11 ms after onset of eye movement; this initial effect was independent of linear acceleration. An otolith mediated effect modified VOR gain depending on both linear acceleration and target distance beginning 25-90 ms after onset of head rotation. For rotational axes anterior to the otoliths, VOR gain for the nearest target was initially higher but later became less than that for the far target. There was no gain correction for the physical separation between the eyes and otoliths. With lower acceleration, there was a nonlinear reduction in the early gain increase with close targets although later otolith-mediated effects were not affected. In subjects with unilateral vestibular deafferentation, the initial VOR was quantitatively normal for rotation toward the intact side. When rotating toward the deafferented side, VOR gain remained less than half of normal for at least the initial 55 ms when head acceleration was highest and was not modulated by target distance. After this initial high acceleration period, gain increased to a degree depending on target distance and axis eccentricity. This behavior suggests that the commissural VOR pathways are not modulated by target distance. These results suggest that the VOR is initially driven by short latency ipsilateral target distance dependent and bilateral target-distance independent canal pathways. After 25 ms, otolith inputs contribute to the target distance dependent pathway. The otolith input later grows to eventually dominate the target distance mediated effect. When otolith input is unavailable the target distance mediated canal component persists. Modulation of canal mediated responses by target distance is a nonlinear effect, most evident for high head accelerations.

Subjective Visual Horizontal During Follow-up After Unilateral Vestibular Deafferentation with Gentamicin

The subjective visual horizontal (SVH) was measured by means of a small, rotatable, luminous line in darkness in the upright head and body position and at 10, 20 and 30° of tilt to the right and left before, and repeatedly during a follow-up period of 1 year after intratympanic gentamicin instillations in 12 patients with recurrent vertigo attacks. This treatment caused a loss of the bithermal caloric responses on the diseased side. Shortly after treatment there was a significant tilt of SVH towards the treated side (group mean=10.6°). Repeated testing made it possible to characterize mathematically the changes with time for SVH. For the group of patients as a whole this otolithic component of vestibular compensation was best described by a power function, SVH=8.65t-0.16 degrees, where t is time in days after maximum tilt of SVH. After 1 year, SVH was still significantly tilted towards the treated side (group mean=3.16°). Gentamicin treatment also caused a significant reduction in the perception of head and body tilt towards the deafferented side, while the perception of tilt towards the healthy side did not show any significant changes. During follow-up there was a gradual improvement in the perception of tilt towards the treated side. However, a significant asymmetry in roll-tilt perception was still present 1 year after deafferentation. There was no correlation between SVH in the upright position and roll-tilt perception, suggesting that these parameters are to some extent dependent on different afferent input from the vestibular organ. They were also found to be complementary for the detection of vestibular disturbance.

The horizontal optokinetic reflex of the opossum (Didelphis marsupialis aurita): physiological and anatomical studies in normal and early monoenucleated specimens.

In the opossum the symmetrical binocular horizontal optokinetic nystagmus gives way to an asymmetrical monocular reflex: the nasotemporal (NT) stimulation yielding lower gain than the temporonasal (TN). In adults, monocularly enucleated at postnatal days 21-25 (pnd21-25), the gain of NT responses is markedly increased, approaching that of TN. Severe cell loss was detected in the nucleus of the optic tract (NOT) on the deafferented side in early monoenucleated specimens. In normal animals retinal afferents to the NOT are all crossed, while in animals enucleated at pnd21-25 sparse uncrossed retinal elements were observed. Although this abnormal projection might influence the increased NT response in this subgroup, it is argued that the increased symmetry in monoenucleated opossums may be the result of changes mediated by the commissural connection between both NOTs.

Destruction of olfactory inputs affects the morphogenesis of the telencephalon in rats.

We unilaterally destroyed the nasal radix of rat embryos on day 15.5 of gestation (E15.5) in utero so as to block the olfactory inputs to the ipsilateral forebrain vesicle. The embryonic brains were examined after 6 days' survival (E21.5). In the deafferented half of the brain, LHRH neurons were significantly reduced in number, indicating the successful blocking of the olfactory input. On the deafferented side, the olfactory bulb failed to develop, and the telencephalic hemisphere, small in size, accompanied various histogenetic retardations in the primary olfactory cortex, in the cortical plate, and in the hippocampal formation. The striatum revealed remarkable structural differences between the ipsilateral and contralateral sides: on the ipsilateral side, the striatum was small in size and displayed numerical reductions of immunoreactive tyrosine hydroxylase (TH) fibers and substance P (SP) neurons in comparison with those in the contralateral one; in the substantia nigra, TH neurons and SP fibers were less numerous on the deafferented side. There were no remarkable differences in the distribution of TH neurons in the hypothalamus. In view of these sequential histogenetic alterations, it can be assumed that the olfactory inputs play a key role in the telencephalic morphogenesis.

Evolution of morphological and histochemical changes in the adult cat cuneate nucleus following forelimb denervation.

Morphological and histochemical changes were studied in the ipsilateral cuneate nucleus between one and 52 weeks after forelimb denervation in adult cats. The deafferented nucleus and neighboring fasciculus were noticeably reduced in size within four weeks and decreased further by 13 weeks. The intensity of acetylcholinesterase staining decreased within one week and was further reduced one month after nerve transections. This reduction in acetylcholinesterase staining was transient, approaching control levels within one year. Parvalbumin immunostaining was also altered by the nerve transections; on the deafferented side, the neuropil staining in the cuneate nucleus and fasciculus decreased, but the number of parvalbumin-positive cells was consistently greater than in the contralateral side. These cell counts returned to normal levels within one year. One month after the injury, cytochrome oxidase activity was reduced. This reduction persisted and was even more apparent after one year. In parallel, the cell clusters of the nucleus became progressively less distinct. These observations in an adult mammal indicate that peripheral nerve injury imposes molecular and morphological changes on second-order sensory neurons which evolve differentially with time. Although some changes developed rapidly after deafferentation, the onset of others was slower; and whereas some seemed irreversible, others eventually regressed. Taken together with the functional studies of others, these findings suggest that early molecular changes observed in cuneate neurons reflect adaptive reactions to lesion-induced alterations in afferent activity. Permanent deprivation of the normal input, however, would eventually lead to chronic, and perhaps irreversible, degenerative changes.

Vestibular neuritis: Clinical-pathologic correlation

Postmortem examination of the brain and temporal bones of a patient with well-documented vestibular neuritis showed selective neuronal loss in Scarpa's ganglia on the side with absent caloric response. There was loss of hair cells and an “epithelialization” of the utricular macule and semicircular canal cristae on the deafferented side, and synaptic density in the vestibular nuclei on the deafferented side was decreased compared with that on the normal side. All findings were consistent with an isolated viral infection of Scarpa's ganglia. This is the first description of the effects of chronic deafferentation on the vestibular sensory epithelia and the vestibular nuclei in a human being. (Otolaryngol Head Neck Surg 1996;114:586-92.)