Effects Of Deafferentation Research Articles

Mitral Cell Dendritic Morphology in the Adult Zebrafish Olfactory Bulb following Growth, Injury and Recovery.

The role of afferent target interactions in dendritic plasticity within the adult brain remains poorly understood. There is a paucity of data regarding the effects of deafferentation and subsequent dendritic recovery in adult brain structures. Moreover, although adult zebrafish demonstrate ongoing growth, investigations into the impact of growth on mitral cell (MC) dendritic arbor structure and complexity are lacking. Leveraging the regenerative capabilities of the zebrafish olfactory system, we conducted a comprehensive study to address these gaps. Employing an eight-week reversible deafferentation injury model followed by retrograde labeling, we observed substantial morphological alterations in MC dendrites. Our hypothesis posited that cessation of injury would facilitate recovery of MC dendritic arbor structure and complexity, potentially influenced by growth dynamics. Statistical analyses revealed significant changes in MC dendritic morphology following growth and recovery periods, indicating that MC total dendritic branch length retained significance after 8 weeks of deafferentation injury when normalized to individual fish physical characteristics. This suggests that regeneration of branch length could potentially function relatively independently of growth-related changes. These findings underscore the remarkable plasticity of adult dendritic arbor structures in a sophisticated model organism and highlight the efficacy of zebrafish as a vital implement for studying neuroregenerative processes.

Blocking tactile input to one finger using anaesthetic enhances touch perception and learning in other fingers.

Brain plasticity is a key mechanism for learning and recovery. A striking example of plasticity in the adult brain occurs following input loss, for example, following amputation, whereby the deprived zone is “invaded” by new representations. Although it has long been assumed that such reorganization leads to functional benefits for the invading representation, the behavioral evidence is controversial. Here, we investigate whether a temporary period of somatosensory input loss to one finger, induced by anesthetic block, is sufficient to cause improvements in touch perception (“direct” effects of deafferentation). Further, we determine whether this deprivation can improve touch perception by enhancing sensory learning processes, for example, by training (“interactive” effects). Importantly, we explore whether direct and interactive effects of deprivation are dissociable by directly comparing their effects on touch perception. Using psychophysical thresholds, we found brief deprivation alone caused improvements in tactile perception of a finger adjacent to the blocked finger but not to non-neighboring fingers. Two additional groups underwent minimal tactile training to one finger either during anesthetic block of the neighboring finger or a sham block with saline. Deprivation significantly enhanced the effects of tactile perceptual training, causing greater learning transfer compared with sham block. That is, following deafferentation and training, learning gains were seen in fingers normally outside the boundaries of topographic transfer of tactile perceptual learning. Our results demonstrate that sensory deprivation can improve perceptual abilities, both directly and interactively, when combined with sensory learning. This dissociation provides novel opportunities for future clinical interventions to improve sensation.

Deafferentation-induced alterations in mitral cell dendritic morphology in the adult zebrafish olfactory bulb.

The removal of afferent input to the olfactory bulb by both cautery and chemical olfactory organ ablation in adult zebrafish results in a significant decrease in volume of the ipsilateral olfactory bulb. To examine the effects of deafferentation at a cellular level, primary output neurons of the olfactory bulb, the mitral cells, were investigated using retrograde tract tracing with fluorescent dextran using ex vivo brain cultures. Morphological characteristics including the number of major dendritic branches, total length of dendritic branches, area of the dendritic arbor, overall dendritic complexity, and optical density of the arbor were used to determine the effects of deafferentation on mitral cell dendrites. Following 8weeks of permanent deafferentation there were significant reductions in the total length of dendritic branches, the area of the dendritic arbor, and the density of fine processes in the dendritic tuft. With 8weeks of chronic, partial deafferentation there were significant reductions in all parameters examined, including a modified Sholl analysis that showed significant decreases in overall dendritic complexity. These results show the plasticity of mitral cell dendritic structures in the adult brain and provide information about the response of these output neurons following the loss of sensory input in this key model system.

Effects of early eye removal on the morphology of a multisensory neuron in the chicken optic tectum

The midbrain is a subcortical area involved in central functions such as integrating sensory modalities, movement initiation and bottom-up and top-down attention. In chicken, the midbrain roof is termed optic tectum (TeO) and consists of 15 layers with distinct in- and output regions. Visual input targets the superficial layers, while auditory input terminates in deeper layers. It has been shown that ablation of sensory epithelia leads to changes in the cellular patterning and structural organization of the sensory pathways. For the tectum, ablation of the eye anlagen was shown to affect retinorecipient neurons. While the gross morphology remained intact after enucleation, the shape of dendritic endings was changed presumably due to missing presynaptic input during synaptic pruning.We investigated the effect of deafferentation in a multisensory cell type, the Shepherd’s crook neuron (SCN) in the TeO. SCNs have distinct dendritic branches in retinorecipient layers (superficial layers 1 to 5 and 7) and in layers where auditory input terminates. To assess whether removal of a single sensory input only affects the dendrites recipient for that input, we removed the eye anlagen and retrogradely labeled SCNs later in embryogenesis to visualize the morphology in lesioned and non-lesioned embryos. We found no changes in the gross morphology or in the basal dendrites, but an altered growth of the fine structures at the apical dendrite of SCNs in the retinorecipient layers. Our data indicate that the neuronal morphology of SCNs is mostly predefined before retinal innervation affect the fine structure.

Magnetic resonance spectroscopy of current hand amputees reveals evidence for neuronal-level changes in former sensorimotor cortex.

Deafferentation is accompanied by large-scale functional reorganization of maps in the primary sensory and motor areas of the hemisphere contralateral to injury. Animal models of deafferentation suggest a variety of cellular-level changes including depression of neuronal metabolism and even neuronal death. Whether similar neuronal changes contribute to patterns of reorganization within the contralateral sensorimotor cortex of chronic human amputees is uncertain. We used functional MRI-guided proton magnetic resonance spectroscopy to test the hypothesis that unilateral deafferentation is associated with lower levels of N-acetylaspartate (NAA, a putative marker of neuronal integrity) in the sensorimotor hand territory located contralateral to the missing hand in chronic amputees (n = 19) compared with the analogous hand territory of age- and sex-matched healthy controls (n = 28). We also tested whether former amputees [i.e., recipients of replanted (n = 3) or transplanted (n = 2) hands] exhibit NAA levels that are indistinguishable from controls, possible evidence for reversal of the effects of deafferentation. As predicted, relative to controls, current amputees exhibited lower levels of NAA that were negatively and significantly correlated with the time after amputation. Contrary to our prediction, NAA levels in both replanted and transplanted patients fell within the range of the current amputees. We suggest that lower levels of NAA in current amputees reflects altered neuronal integrity consequent to chronic deafferentation. Thus local changes in NAA levels may provide a means of assessing neuroplastic changes in deafferented cortex. Results from former amputees suggest that these changes may not be readily reversible through reafferentation.NEW & NOTEWORTHY This study is the first to use functional magnetic resonance-guided magnetic resonance spectroscopy to examine neurochemical mechanisms underlying functional reorganization in the primary somatosensory and motor cortices consequent to upper extremity amputation and its potential reversal through hand replantation or transplantation. We provide evidence for selective alteration of cortical neuronal integrity associated with amputation-related deafferentation that may not be reversible.

Altered Spatiotemporal Dynamics of Cortical Activation to Tactile Stimuli in Somatosensory Area 3b and Area 1 of Monkeys after Spinal Cord Injury.

Reactivation of deafferented cortex plays a key role in mediating the recovery of lost functions, although the precise mechanism is not fully understood. This study simultaneously characterized the dynamic spatiotemporal features of tactile responses in areas 3b and 1 before and 6–8 weeks after partial dorsal column lesion (DCL), and examined how the reactivation relates to the recovery of simple hand use in squirrel monkeys. A combination of high spatiotemporal resolution functional intrinsic optical imaging, microelectrode mapping, behavioral assessment, and tracer histology methods were used. Compared with the normal cortex, we found that the responses of deafferented areas 3b and 1 to 3 s of continuous 8 Hz tactile stimulation of a single digit were significantly weaker and more transient. This finding indicates a loss of response to sustained tactile stimuli. The activation area enlarged for areas 3b and 1 in both directions along digit representation (medial–lateral) and across areas (anterior–posterior). All subjects showed behavioral deficits in a food reaching-grasping-retrieving task within the first 5 weeks after DCL, but recovered at the time when optical images were acquired. Summarily, we showed that these populations of cortical neurons responded to peripheral tactile inputs, albeit in significantly altered manners in each area, several weeks after deafferentation. We propose that compromised ascending driven inputs, impaired lateral inhibition, and local integration of input signals may account for the altered spatiotemporal dynamics of the reactivated areas 3b and 1 cortices. Further investigation with large sample sizes is needed to fully characterize the effects of deafferentation on area 1 activation size.

Reorganization of Synaptic Connections and Perineuronal Nets in the Deep Cerebellar Nuclei of Purkinje Cell Degeneration Mutant Mice.

The perineuronal net (PN) is a subtype of extracellular matrix appearing as a net-like structure around distinct neurons throughout the whole CNS. PNs surround the soma, proximal dendrites, and the axonal initial segment embedding synaptic terminals on the neuronal surface. Different functions of the PNs are suggested which include support of synaptic stabilization, inhibition of axonal sprouting, and control of neuronal plasticity. A number of studies provide evidence that removing PNs or PN-components results in renewed neurite growth and synaptogenesis. In a mouse model for Purkinje cell degeneration, we examined the effect of deafferentation on synaptic remodeling and modulation of PNs in the deep cerebellar nuclei. We found reduced GABAergic, enhanced glutamatergic innervations at PN-associated neurons, and altered expression of the PN-components brevican and hapln4. These data refer to a direct interaction between ECM and synapses. The altered brevican expression induced by activated astrocytes could be required for an adequate regeneration by promoting neurite growth and synaptogenesis.

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

Abstract WP216: Cortical Network Dynamics in Acute Ischemic Stroke

INTRODUCTION: Measures of brain function are a unique source of insight into stroke effects, but the most commonly used methods (fMRI, PET) are difficult to implement in acutely ill patients, and so little is known about changes in brain function in the days after stroke. Advances in dense-array electroencephalography (dEEG) make possible the study of cortical network dynamics at the bedside. The current study addressed the hypothesis that changes in the motor network are measurable in first days post-stroke, and that these network changes are related to behavioral deficits. METHODS: Nine patients with acute (&lt;120 hours) ischemic stroke underwent dEEG and behavioral testing that included Box &amp; Blocks score (1 min). The dEEG signals from 256 scalp leads were recorded at 1000Hz, along with bilateral forearm EMG, during cued 0.14 Hz wrist flexions. Nine age-matched healthy controls underwent the same assessments. Cortical network dynamics were assessed in the motor system using EEG coherence between leads, focusing on β range (20-30 Hz) signals. Spectral power in this range was also obtained. RESULTS: Patients were 62±13 years old, with median NIHSS score=3 (range 1-12), and could move 26±18 blocks (range 0-50) on the Box &amp; Blocks test, fewer than controls (59±7 blocks, p&lt;0.0001). In patients, as compared to controls, the region overlying ipsilesional hand motor cortex showed increased coherence with [A] contralesional hand motor cortex (0.13±0.06 vs 0.07±0.05, p=0.03) and [B] supplementary motor area (0.27±0.12 vs 0.15±0.07, p=0.02) during flexion of the affected wrist. Spectral power did not differ between groups in these regions. Across all subjects, the magnitude of coherence between hand motor cortex and supplementary motor area was inversely related to Box &amp; Blocks score (r=-0.61, p=0.008). CONCLUSIONS: Assessment of cortical dynamics in the motor system is feasible in the acute stroke setting, with hemiparetic patients demonstrating significantly increased β coherence. Increased EEG coherence between two motor cortex regions after stroke might reflect increased functional connectivity due to the reduced cortical inhibition that is seen early after stroke, effects of deafferentation, or increased input from a common area such as the thalamus.

Olfactory bulb recovery following reversible deafferentation with repeated detergent application in the adult zebrafish

The neuroplasticity and regenerative properties of the olfactory system make it a useful model for studying the ability of the nervous system to recover from damage. We have developed a novel method for examining the effects of long-term deafferentation and regeneration of the olfactory organ and resulting influence on the olfactory bulb in adult zebrafish. To test the hypothesis that repeated damage to the olfactory epithelium causes reduced olfactory bulb afferent input and cessation of treatment allows recovery, we chronically ablated the olfactory organ every 2-3 days for 3 weeks with the detergent Triton X-100 while another group was allowed 3 weeks of recovery following treatment. Animals receiving chronic treatment showed severe morphological disruption of the olfactory organ, although small pockets of epithelium remained. These pockets were labeled by anti-calretinin, indicating the presence of mature olfactory sensory neurons (OSNs). Following a recovery period, the epithelium was more extensive and neuronal labeling increased, with three different morphologies of sensory neurons observed. Repeated peripheral exposure to Triton X-100 also affected the olfactory bulb. Bulb volumes and anti-tyrosine hydroxylase-like immunoreactivity, which is an indicator of afferent activity, were diminished in the olfactory bulb of the chronically treated group compared to the control side. In the recovery group, there was little difference in bulb volume or antibody staining. These results suggest that repeated, long-term nasal irrigation with Triton X-100 eliminates a substantial number of mature OSNs and reduces afferent input to the olfactory bulb. It also appears that these effects are reversible and regeneration will occur in both the peripheral olfactory organ and the olfactory bulb when given time to recover following cessation of treatment. We report here a new method that allows observation not only of the effects of deafferentation on the olfactory bulb but also the effects of reinnervation.

Pre-operative vestibular pattern and balance compensation after vestibular schwannoma surgery

This longitudinal study aimed to assess the sensorimotor balance strategies before and after vestibular schwannoma (VS) surgery according to the degree of pre-operative vestibular lesion. Thirty-eight VS patients were split in three groups according to caloric vestibular test results before surgery; nine had a symmetrical vestibular response (vestibular normoreflexy), 19 with a decreased response of more than 20% of the affected side (vestibular hyporeflexy) and 10 with an absent caloric response on the side of the affected labyrinth (vestibular areflexy). They underwent pendular rotary vestibular testing (RVT), allowing to evaluate gain and directional preponderance of the vestibulo-ocular reflex, and a sensory organisation test (SOT), evaluating balance control in six conditions (C1 to C6). These tests were performed shortly before, and 8 and 90 days after surgery. Directional preponderance performances of patients with vestibular normoreflexy or hyporeflexy followed a classical time-course with a huge asymmetry just after surgery and a recovery to pre-operative performances at 90 days; patients with vestibular areflexy were relatively stable in time. Variation in SOT performances of patients with vestibular normoreflexy, especially in the more complex C4 to C6, followed a classical time-course with an important postural degradation just after surgery and a recovery to pre-operative performances at 90 days. Patients with vestibular areflexy showed no balance degradation just after surgery and a marked increase in performances at 90 days after surgery, especially in C5 and C6. Performances of patients with vestibular hyporeflexy were intermediate, close to performances of patients with vestibular normoreflexy before surgery and close to performances of patients with vestibular areflexy at 8 and 90 days after surgery. Pre-operative vestibular function alteration triggers an adaptive process, characterized by a restoration of the symmetry of the vestibular nuclei activity and by sensory substitution and new behavioural strategies, allowing the anticipation of unilateral vestibular deafferentation effects.

Spontaneous movements: Effect of denervation and relation to the adaptation of nociceptive withdrawal reflexes in the rat

Spontaneous movements are a ubiquitous phenomenon during development. Recently, we demonstrated that these movements play a key role in the functional adaptation of spinal reflex circuits. Here, we analyse the role of afferent input in the generation of spontaneous movements and characterize the occurrence of different types of spontaneous movements and their relation to the functional adaptation of the nociceptive withdrawal reflexes (NWR) up to postnatal day 22 (P22). Noxious thermal stimulation was used to evoke reflex responses in awake rats. Spontaneous tail movements occurring during active sleep were counted during the first three postnatal weeks and classified into two major classes: simple movements (unidirectional) and complex twitches (bi-directional and oscillating). All spinal nerves caudal to L2 were cut at P12 to study the effect of deafferentation on spontaneous movements. The number of simple movements and complex twitches in the deafferented animals did not differ as compared to control animals. The adaptation of tail NWR occurred during the period P7–P22. Spontaneous tail movements occurred relatively frequently and overlapped in time the adaptation of NWR. Notably, the relative number of simple movements increased in parallel with the functional adaptation of the NWR, suggesting a role of simple twitches in NWR adaptation. The present findings indicate that the spontaneous movements studied are driven by intrinsic mechanisms in the CNS and suggest that sensory feedback does not influence the spontaneous movement patterns. Moreover, the NWR adaptation appears to be related to a qualitative change in spontaneous movements caused by maturation in spinal reflex circuit connections.

Selective vulnerability of adult cochlear nucleus neurons to de-afferentation by mechanical compression

It is well established that the cochlear nucleus (CN) of developing species is susceptible to loss of synaptic connections from the auditory periphery. Less information is known about how de-afferentation affects the adult auditory system. We investigated the effects of de-afferentation to the adult CN by mechanical compression. This experimental model is quantifiable and highly reproducible. Five weeks after mechanical compression to the axons of the auditory neurons, the total number of neurons in the CN was evaluated using un-biased stereological methods. A region-specific degeneration of neurons in the dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) by 50% was found. Degeneration of neurons in the anteroventral cochlear nucleus (AVCN) was not found. An imbalance between excitatory and inhibitory synaptic transmission after de-afferentation may have played a crucial role in the development of neuronal cell demise in the CN. The occurrence of a region-specific loss of adult CN neurons illustrates the importance of evaluating all regions of the CN to investigate the effects of de-afferentation. Thus, this experimental model may be promising to obtain not only the basic knowledge on auditory nerve/CN degeneration but also the information relevant to the application of cochlear or auditory brainstem implants.

Topography and axon arbor architecture in the visual callosal pathway: effects of deafferentation and blockade of TV-methyl-D-aspartate receptors

Visual callosal fibers link cortical loci in opposite hemispheres that represent the same visual field but whose locations are not mirror-symmetric with respect to the brain midline. Presence of the eyes from postnatal day 4 (P4) to P6 is required for this map to be specified. We tested the hypothesis that specification of the callosal map requires the activation of N-methyl-D-aspartate receptors (NMDARs). Our results show that blockade of NMDARs with MK-801 during this critical period did not induce obvious abnormalities in callosal connectivity patterns, suggesting that retinal influences do not operate through NMDAR-mediated processes to specify normal callosal topography. In contrast, we found that interfering with NMDAR function either through MK801-induced blockade of NMDARs starting at P6 or neonatal enucleation significantly increases the length of axon branches and total length of arbors, without major effects on the number of branch tips. Our results further suggest that NMDARs act by altering the initial elaboration of arbors rather than by inhibiting a later-occurring remodeling process. Since the callosal map is present by P6, just as axonal branches of simple architecture grow into gray matter, we suggest that regulation of arbor development by NMDAR-mediated processes is important for maintaining the precision of this map.

Topography and axon arbor architecture in the visual callosal pathway: effects of deafferentation and blockade of N-methyl-D-aspartate receptors.

Visual callosal fibers link cortical loci in opposite hemispheres that represent the same visual field but whose locations are not mirror-symmetric with respect to the brain midline. Presence of the eyes from postnatal day 4 (P4) to P6 is required for this map to be specified. We tested the hypothesis that specification of the callosal map requires the activation of N-methyl-D-aspartate receptors (NMDARs). Our results show that blockade of NMDARs with MK-801 during this critical period did not induce obvious abnormalities in callosal connectivity patterns, suggesting that retinal influences do not operate through NMDAR-mediated processes to specify normal callosal topography. In contrast, we found that interfering with NMDAR function either through MK801-induced blockade of NMDARs starting at P6 or neonatal enucleation significantly increases the length of axon branches and total length of arbors, without major effects on the number of branch tips. Our results further suggest that NMDARs act by altering the initial elaboration of arbors rather than by inhibiting a later-occurring remodeling process. Since the callosal map is present by P6, just as axonal branches of simple architecture grow into gray matter, we suggest that regulation of arbor development by NMDAR-mediated processes is important for maintaining the precision of this map.

Deafferentation of neighbouring motor cortex areas does not further enhance saturated practice-dependent plasticity in healthy adults

Objective To assess effects of deafferentation of the arm representation of primary motor cortex (M1) on practice-dependent plasticity in healthy adults. Methods Twelve healthy, right-handed adults (18–48 years, median 20.2 years) performed two consecutive experiments (exp. 1 and exp. 2). Exp. 1 consisted of a motor practice (MP) of repeated ballistic flexion movements of the left thumb. This was followed by exp. 2 consisting of selective anaesthesia of the upper brachial plexus (SPA) to disinhibit the training M1 and a second period of the same MP. Peak acceleration of the trained thumb movement and the motor evoked potential (MEP) amplitude in the flexor pollicis brevis muscle elicited by single-pulse transcranial magnetic stimulation of the training M1 were studied before and after exp. 1 and after exp. 2. Results After exp. 1 all subjects demonstrated an increase of peak acceleration (baseline: 19.23 ± 3.81 m s −2; after exp. 1: 43.28 ± 17.63 m s −2, p = 0.008) and MEP amplitude (from 0.46 ± 0.23 mV to 1.26 ± 0.77 mV, p = 0.03). There was no additional increase of these measures after exp. 2 (44.37 ± 19.56 m s −2, p = 0.78, 1.69 ± 1.21 mV ( p = 0.07)). Conclusions Training of ballistic thumb movements leads to behavioural improvement as well as to an increased excitability of the corresponding M1 representation. These effects do not increase further during deafferentation of the training M1. In contrast to stroke patients [Muellbacher W, Richards C, Ziemann U, Wittenberg G, Weltz D, Boroojerdi B, et al. Improving hand function in chronic stroke. Arch Neurol 2002;59:1278–82], practice-dependent plasticity in healthy subjects cannot be enhanced by deafferentation of neighbouring motor cortex areas. Significance Healthy subjects, in contrast to patients with central motor lesions, are capable of saturating practice-dependent plasticity to a level that cannot be further enhanced by experimental manipulation.

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.

Central and Sensory Contributions to the Activation and Organization of Muscle Synergies during Natural Motor Behaviors

Previous studies have suggested that the motor system may simplify control by combining a small number of muscle synergies represented as activation profiles across a set of muscles. The role of sensory feedback in the activation and organization of synergies has remained an open question. Here, we assess to what extent the motor system relies on centrally organized synergies activated by spinal and/or supraspinal commands to generate motor outputs by analyzing electromyographic (EMG) signals collected from 13 hindlimb muscles of the bullfrog during swimming and jumping, before and after deafferentation. We first established that, for both behaviors, the intact and deafferented data sets possess low and similar dimensionalities. Subsequently, we used a novel reformulation of the non-negative matrix factorization algorithm to simultaneously search for synergies shared by, and synergies specific to, the intact and deafferented data sets. Most muscle synergies were identified as shared synergies, suggesting that EMGs of locomotor behaviors are generated primarily by centrally organized synergies. Both the amplitude and temporal patterns of the activation coefficients of most shared synergies, however, were altered by deafferentation, suggesting that sensory inflow modulates activation of those centrally organized synergies. For most synergies, effects of deafferentation on the activation coefficients were not consistent across frogs, indicating substantial interanimal variability of feedback actions. We speculate that sensory feedback might adapt recruitment of muscle synergies to behavioral constraints, and the few synergies specific to the intact or deafferented states might represent afferent-specific modules or feedback reorganization of spinal neuronal networks.

Effect of neonatal spinal transection and dorsal rhizotomy on hindlimb muscles

The purpose of this study was to elucidate the effect of deafferentation on spinal motoneurons. We studied the effects of spinal cord transection and/or dorsal rhizotomy upon the contractile properties of EDL and soleus muscle, as well as on the number of motoneurons corresponding to these muscles. Neonatal Wistar rats were randomly divided into four groups in which spinal midthoracic section (T8–T10), unilateral dorsal lumbar rhizotomy (L3–S2) or both procedures were performed on the second postnatal day (PND2). Another group served as unoperated control. At 2 months of age, the animals were evaluated for the contractile properties of a fast (EDL) and a slow (soleus) muscle. Isometric tension recordings were elicited by way of sciatic nerve branches stimulation. In addition, the incremental method was applied for the determination of the number of motor units supplying the two muscles, which was also verified by using the horseradish peroxidase (HRP) method of reverse labeling of motoneurons. Muscle alterations were confirmed by the usual biochemical staining. Our results, in agreement with the data from other researchers, show that significant muscle atrophy takes place after all experimental procedures. Additionally, spinal cord section alters the development of the dynamic properties of soleus muscle, which attains a fast profile. Following transection, the number of motor units remained unaltered, while rhizotomy affected only the soleus by reducing its motor units. The combined procedure affected both muscles, indicating that adequate synaptic input is essential for motoneuron survival.

Neurotrophin‐3 null mutant mice display a postnatal motor neuropathy

This paper examines early postnatal development of the neuromuscular system in mice with a null mutation in the gene for neurotrophin-3. We report that alpha-motoneurons at first develop substantially normally, despite a known 15% deficit in their somal size [Woolley et al. (1999)Neurosci. Lett., 272, 107-110.] and the absence of proprioceptive input [Ernfors et al. (1994)Cell, 77, 503-512]. At birth, motor axons have extended into the muscle, forming normal-looking neuromuscular junctions with focal accumulations of acetylcholine receptors. Detailed ultrastructural analysis does however, reveal subtle abnormalities at this time, particularly a decrease in the extent of occupancy of the postsynaptic site by nerve terminals, and a small but significant deficit in myofibre number. After the relative normality of this early neuromuscular development, there then occurs a catastrophic postnatal loss of motor nerve terminals, resulting in complete denervation of hindlimb muscles by P7. In systematic semi-serial samples through the entire muscle endplate zones, no neuromuscular junctions can be found. Intramuscular axons are fragmented, as shown by both electron microscopic observations and neurofilament immunohistochemistry, and alpha-bungarotoxin detection of acetylcholine receptors indicates dispersal of the junctional accumulation. At earlier times (postnatal days three and four) the terminal Schwann cells show ultrastructural abnormalities, and preliminary observations suggest marked disturbance of myelination. Based on comparison with other literature, the peripheral nerve degeneration seems unlikely to have arisen as a secondary effect of de-afferentation. We discuss whether the neural degeneration is secondary to the disturbance of Schwann cell function, or due directly to a loss of neurotrophin-3 based support of the motoneuron.