Geometrical differences between neck motoneurons located in the brainstem and spinal cord in the mallard Anas platyrhynchos L.; a Golgi study.

The dendrite geometry of neck motoneurons located in the upper cervical cord and lower brainstem of the mallard was studied in Golgi silver impregnated material. Measurements were obtained from camera lucida drawings and concerned the extent and orientation of dendritic trees. Dendrites were found to be oriented predominantly parallel to the sagittal plane, and projections were asymmetric in the dorso-ventral direction. Comparison between motoneurons located in the supraspinal nucleus of the brainstem and motoneurons in the ventral horn of the upper spinal cord showed that dendrites of motoneurons in the first cell group branch more often than those of neurons in the latter group. In addition, dendritic trees of ventral horn motoneurons preferentially project into the field dorsal to the cell body.     

谷氨酸转运抑制剂对器官型培养脊髓片的影响

观察谷氨酸转运体抑制剂苏一羟天冬氨酸(Threo-hydroxyaspartate,THA)对器官型培养的脊髓片的影响,探讨谷氨酸在运动神经元损伤中的作用。取出生后8天乳鼠的腰段脊髓组织切片做脊髓器官型培养,在培养液中加入不同浓度THA(50μmol／L、100μmol／L、5001μmol／L),用神经元的特异性免疫组化染色剂SMI-32,非磷酸化神经丝标记物,对脊髓腹角α运动神经元进行鉴定,用单克隆抗钙网膜蛋白(calretinin)抗体对背角中间神经元进行记数,测定培养液中乳酸脱氢酶(LDH)的含量,并与对照组比较。结果显示对照组α运动神经元数目恒定,THA可以引起剂量依赖性的培养液中LDH含量增高和α运动神经元数目减少,而脊髓背角的中间神经元损伤相对较轻,其中THA100μmol／L组在体外培养4周后出现类似于肌萎缩侧索硬化(ALS)的病理改变：α运动神经元数目较对照组明显减少,而脊髓背角的中间神经元数目无显著变化。细胞外谷氨酸增高主要对运动神经元造成损伤,脊髓运动神经元较感觉神经元对谷氨酸的兴奋毒作用更加敏感。     

Morphology of lumbar-projecting lateral vestibulospinal neurons in the brainstem and cervical spinal cord in the squirrel monkey

The lateral vestibulospinal tract (LVST) is one of the major descending pathways controlling the extensor musculature of the body. To determine whether individual LVST neurons terminating in the lumbosacral spinal segments issue collaterals more rostrally to exert an influence of the cervical ventral horn intracellular recording and biocytin labeling techniques were used in the squirrel monkey. Only neurons monosynaptically related to the 8th nerve and antidromically identified to project below T12 were selected for study. The axon course through the brainstem and cervical spinal cord was examined in 37 LVST neurons. The average distance of recovered axon was 17.3 mm (4.5-31.7 mm). None could be antidromically activated from shocks applied to the rostral medial longitudinal fasciculus near the 3rd nuclei; and no collaterals were observed in the brainstem. Of the 37 neurons, only 1 axon issued a collateral to innervate the ventral horn, primarily in the region of the spinal accessory motoneurons; this single collateral provided a relatively minor input compared to that of LVST neurons terminating in the cervical cord. Thus, secondary, caudal-projecting LVST neurons represent a private, and mostly rapid, communication pathway between dorsal Deiters' nucleus and the motor circuits controlling the lower limbs and tail.     

Modulation of Matrix Metalloproteinases Activity in the Ventral Horn of the Spinal Cord Re-stores Neuroglial Synaptic Homeostasis and Neurotrophic Support following Peripheral Nerve Injury

Modulation of extracellular matrix (ECM) remodeling after peripheral nerve injury (PNI) could represent a valid therapeutic strategy to prevent maladaptive synaptic plasticity in central nervous system (CNS). Inhibition of matrix metalloproteinases (MMPs) and maintaining a neurotrophic support could represent two approaches to prevent or reduce the maladaptive plastic changes in the ventral horn of spinal cord following PNI. The purpose of our study was to analyze changes in the ventral horn produced by gliopathy determined by the suffering of motor neurons following spared nerve injury (SNI) of the sciatic nerve and how the intrathecal (i.t.) administration of GM6001 (a MMPs inhibitor) or the NGF mimetic peptide BB14 modulate these events. Immunohistochemical analysis of spinal cord sections revealed that motor neuron disease following SNI was associated with increased microglial (Iba1) and astrocytic (GFAP) response in the ventral horn of the spinal cord, indicative of reactive gliosis. These changes were paralleled by decreased glial aminoacid transporters (glutamate GLT1 and glycine GlyT1), increased levels of the neuronal glutamate transporter EAAC1, and a net increase of the Glutamate/GABA ratio, as measured by HPLC analysis. These molecular changes correlated to a significant reduction of mature NGF levels in the ventral horn. Continuous i.t. infusion of both GM6001 and BB14 reduced reactive astrogliosis, recovered the expression of neuronal and glial transporters, lowering the Glutamate/GABA ratio. Inhibition of MMPs by GM6001 significantly increased mature NGF levels, but it was absolutely ineffective in modifying the reactivity of microglia cells. Therefore, MMPs inhibition, although supplies neurotrophic support to ECM components and restores neuro-glial transporters expression, differently modulates astrocytic and microglial response after PNI.     

Spatial and temporal relationship between monocyte chemoattractant protein-1 expression and spinal glial activation following peripheral nerve injury

Peripheral nerve injury can induce spinal microglial/astrocyte activation. Substances released by activated glial cells excite spinal nociceptive neurons. Pharmacological disruption of glial activation or antagonism of substances released by activated glia prevent or reverse pain hypersensitivity. It is not known, however, what causes spinal cord glia to shift from a resting to an activated state. In an attempt to understand the potential role of monocyte chemoattractant protein-1 (MCP-1) in triggering spinal glial activation and its contribution to the development of neuropathic pain, we investigated the effect of peripheral nerve injury on MCP-1 expression in dorsal root ganglia (DRG) and the spinal cord, and established its temporal relationship with activation of spinal microglia and astrocytes. We observed that MCP-1 was induced by chronic constriction of the sciatic nerve in DRG sensory neurons, spinal cord motor neurons and in the superficial dorsal horn, ipsilateral to the injury. Neuronal MCP-1 induction was followed by surrounding microglial activation. After peaking at day 7 after injury, MCP-1 levels began to decline rapidly and had returned to baseline by day 150. In contrast, microglial activation peaked by day 14 and declined afterwards to reach a lower, yet significantly raised level beyond day 22 and remained increased until the end of the test period. Astrocyte activation became detectable later, progressed more slowly and also remained increased until the end of the test period, in parallel with a decreased nociceptive threshold. Our results suggest that neuronal MCP-1 may serve as a trigger for spinal microglial activation, which participates in the initiation of neuropathic pain. Delayed, sustained astrocyte activation may participate with microglia in the persistent phase of pain hypersensitivity.     

Development of spinal motor networks in the chick embryo.

We have examined the cellular and synaptic mechanisms underlying the genesis of alternating motor activity in the developing spinal cord of the chick embryo. Experiments were performed on the isolated lumbosacral cord maintained in vitro. Intracellular and whole cell patch clamp recordings obtained from sartorius (primarily a hip flexor) and femorotibialis (a knee extensor) motoneurons showed that both classes of cell are depolarized simultaneously during each cycle of motor activity. Sartorius motoneurons generally fire two bursts/cycle, whereas femorotibialis motoneurons discharge throughout their depolarization, with peak activity between the sartorius bursts. Voltage clamp recordings revealed that inhibitory and excitatory synaptic currents are responsible for the depolarization of sartorius motoneurons, whereas femorotibialis motoneurons are activated principally by excitatory currents. Early in development, the dominant synaptic currents in rhythmically active sartorius motoneurons appear to be inhibitory so that firing is restricted to a single, brief burst at the beginning of each cycle. In E7-E13 embryos, lumbosacral motor activity could be evoked following stimulation in the brainstem, even when the brachial and cervical cord was bathed in a reduced calcium solution to block chemical synaptic transmission. These findings suggest that functional descending connections from the brainstem to the lumbar cord are present by E7, although activation of ascending axons or electrical synapses cannot be eliminated. Ablation, optical, and immunocytochemical experiments were performed to characterize the interneuronal network responsible for the synaptic activation of motoneurons. Ablation experiments were used to show that the essential interneuronal elements required for the rhythmic alternation are in the ventral part of the cord. This observation was supported by real-time Fura-2 imaging of the neuronal calcium transients accompanying motor activity, which revealed that a high proportion of rhythmically active cells are located in the ventrolateral part of the cord and that activity could begin in this region. The fluorescence transients in the majority of neurons, including motoneurons, occurred in phase with ventral root or muscle nerve activity, implying synchronized neuronal action in the rhythm generating network. Immunocytochemical experiments were performed in E14-E16 embryos to localize putative inhibitory interneurons that might be involved in the genesis or patterning of motor activity. The results revealed a pattern similar to that seen in other vertebrates with the dorsal horn containing neurons with gamma-aminobutyric acid (GABA)-like immunoreactivity and the ventral and intermediate regions containing neurons with glycine-like immunoreactivity.     

Role of calpain in spinal cord injury: Increased calpain immunoreactivity in rat spinal cord after impact trauma

Impact spinal cord injury (20 g-cm) was induced in rat by weight drop. The immunoreactivity of mcalpain was examined in the lesion and adjacent areas of the cord following trauma. Increased calpain immunoreactivity was evident in the lesion compared to control and the immunostaining intensity progressively increased after injury. The calpain immunoreactivity was also increased in tissue adjacent to the lesion. mCalpain immunoreactivity was significantly stronger in glial and endothelial cells, motor neurons and nerve fibers in the lesion. The calpain immunoreactivity also increased in astrocytes and microglial cells in the adjacent areas. Proliferation of microglia and astrocytes identified by GSA histochemical staining and GFAP immunostaining, respectively, was seen at one and three days after injury. Many motor neurons in the ventral horn showed increased calpain immunoreactivity and were shrunken in the lesion. These studies indicate a pivotal role for calpain and the involvement of glial cells in the tissue destruction in spinal cord injury. Special issue dedicated to Dr. Marion E. Smith.     

Distribution of dipeptidyl peptidase II (Dpp II) in rat spinal cord

The histochemical localization of dipeptidyl peptidase II (Dpp II; E.C. 3.4.14.2) activity was demonstrated at the light microscope level in the rat spinal cord. Prominent staining was observed in motoneurons of the ventral horn and in medium to large neurons in the deep laminae of the dorsal horn, the intermediate gray, and in lamina X surrounding the spinal canal. Within neurons, Dpp II was localized largely in cell perikarya and large primary dendrites with no staining observed in cell nuclei. Neurons in the superficial dorsal horn lack Dpp II enzyme activity. Nonneuronal elements which also stained prominently were pericytes associated with blood vessels and ependymal cells lining the lumen of the spinal canal. A few oligodendrocytes and astrocytes were also stained, but they represented a minor component of the total amount of Dpp II activity. Following ventral root injury, Dpp-II-containing motoneurons degenerate; some glial cells in the region of degenerating neurons become Dpp II positive. The localized distribution of Dpp II in spinal cord neurons suggests that this proteolytic enzyme may play a role in the metabolism of an unidentified neuropeptide.     

Transient expression of Bis protein in midline radial glia in developing rat brainstem and spinal cord

Bis (Bcl-2 interacting death suppressor) has been reported to contribute to the differentiation and maturation of specific neuronal populations in the developing rat forebrain, in addition to its well-established functions as a stress or survival-related protein. In the present study, we have analyzed the expression of Bis in the rat brainstem and cervical spinal cord during development by using immunohistochemistry. Bis immunoreactivity was detected in radial glial cells flanking the midline from embryonic day 14. During embryonic and early postnatal development, Bis expression persisted in differentiating radial glia at the midline but disappeared first in the spinal cord by postnatal day 7 (P7) and later also in the brainstem by P14. Bis expression was restricted to a subpopulation of the midline radial glia, i.e., the dorsal midline of the midbrain and spinal cord and the ventral midline of the hindbrain, which were double- or triple-labeled with vimentin and nestin, markers for radial glia, and S100B. However, these markers also labeled all radial glia including the ventral midline glia in the midbrain and spinal cord, with Bis being absent from these structures. In addition, the dorsal midline glia in the midbrain and spinal cord expressed Bis prior to the timing of expression for radial glial markers. Therefore, our results demonstrate the early and transient expression of Bis in the subpopulation of midline glia in the developing brainstem and spinal cord, suggesting that Bis has a unique role in association with the radial glial cells in the developing central nervous system. This research was supported by a grant (10029970) from the Ministry of Knowledge Economy, The Republic of Korea and by a grant (M103KV010010-08 K2201-01010) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, The Republic of Korea.     

Thyrotropin-Releasing Hormone Enhances Choline Acetyltransferase and Creatine Kinase in Cultured Spinal Ventral Horn Neurons

The effect of 0.1 mM thyrotropin-releasing hormone (TRH) on ventral horn neurons was investigated in eight experimental sets of tissue cultures established from ventral and dorsal portions of spinal cords of 13-15-day rat embryos. Cultures were treated with TRH from day 1 for 2-5 weeks. TRH-treated ventral spinal cord cultures (VSCC), compared with control VSCC, had more numerous and more healthy-appearing neurons and thicker bundles of long cell processes. In TRH-treated VSCC, choline acetyltransferase (ChAT) activity was greater than 16 times (p less than 0.005) and creatine kinase greater than 3 times (p less than 0.005) that of control VSCC. Morphologic and biochemical parameters of dorsal spinal cord cultures remained unchanged by TRH treatment. Since lower motor neurons are numerous in the ventral spinal cord (and not present in the dorsal cord) and since lower motor neurons are the major ChAT-containing spinal cord cells, our data demonstrating a beneficial effect of TRH on VSCC suggest a tropic effect of TRH on lower motor neurons.     

TOPOCHEMICAL ASPECTS OF NUCLEIC ACID AND PROTEIN METABOLISM WITHIN THE NEURON-NEUROGLIA UNIT OF THE SPINAL CORD ANTERIOR HORN

Abstract— Using a two-wavelength modification of ultraviolet and visible cytospectro-photometric methods, the content of nucleic acids per cell was determined in neuronal cytoplasm and glial satellite cell-bodies from the spinal cord anterior horns in mice and rats. Mice which had been swimming for 3 and 4 h showed an increase in the content of RNA in the spinal motoneurons with no changes in the neuroglia. Stronger stimulation of the nervous system such as electrical skin irritation (20-40 V, approx. 40 impulses/min) for 5 min resulted in an increase of RNA in the motoneurons of rat spinal cord and a decrease in the surrounding glia. Exhausting actions upon the nervous system (60 min irritation of rat paws by the electrical current, acute clonic convulsions in rats injected with cardiazol (pentamethylenetetrazol, metrazol) or initial free motor activity after 3 weeks of restraint of mice) induced a marked decrease of RNA content throughout the whole neuron-neuroglia unit. After stimulation, return to normal amounts of RNA and protein was more rapid in glia than in neurons. After 1-3 days rest the level of RNA was normal in motoneurons, but a decrease in glial RNA was shown. These trace changes in the glia are believed to reflect an adaptation mechanism in the nervous system at the cellular level. The relationship between neuronal and glial compartments within the neuron-neuroglia unit is discussed; a supporting, homeostatic, secondary role of glial metabolism with respect to adequate reconstruction of neuronal metabolism is outlined.     

The dorsomedial nuclear group of cranial nerves in the frog.

The dorsomedial motor nuclei were demonstrated by the cobalt-labeling technique applied to the so-called somatic motor cranial nerves. The motoneurons constituting these nuclei are oval-shaped and smaller than the motoneurons in the ventrolateral motor nuclei. They give rise to ventral and dorsal dendrite groups which have extensive arborization areas. A dorsolateral cell group in the rostral three quarters of the oculomotorius nucleus innervates ipsilateral eye muscles (m.obl.inf., m.rect.inf., m.rect.med.) and a ventromedial cell group innervates the contralateral m. rectus superior. Ipsilateral axons originate from ventral dendrites, contralateral axons emerge from the medial aspect of cell bodies, or from dorsal dendrites, and form a "knee" as they turn around the nucleus on their way to join the ipsilateral axons. A few labeled small cells found dorsal and lateral to the main nucleus in the central gray matter are regarded as representing the nucleus of Edinger-Westphal. The trochlearis nucleus is continuous with the ventromedial cell group of the oculomotorius nucleus. The axons originate in dorsal dendrites, run dorsally along the border of the gray matter and pierce the velum medullare on the contralateral side. A compact dendritic bundle of oculomotorius neurons traverse the nucleus, and side branches appear to be in close apposition to the trochlearis neurons. A dorsomedial and a ventrolateral cell group becomes labeled via the abducens nerve. The former supplies the m. rectus lateralis, while the latter corresponds to the accessorius abducens nucleus which innervates the mm. rectractores. Neurons in this latter nucleus are large and multipolar, resembling the neurons in the ventrolateral motor nuclei. Their axons originate from dorsal dendrites and form a "knee" around the dorsomedial aspect of the abducens nucleus. Cobalt applied to the hypoglossus nerve reaches a dorsomedial cell group (the nucleus proper), spinal motoneurons and sympathetic preganglionic neurons. Of the dorsomedial motor cells, the hypoglossus neurons are the largest, and a branch of their ventral dendrites terminates on the contralateral side. Some functional and developmental biological aspects of the morphological findings, such as the crossing axons and the peculiar morphology of the accessory abducens nucleus, are discussed.     

Progesterone neuroprotection in spinal cord trauma involves up-regulation of brain-derived neurotrophic factor in motoneurons

Progesterone (PROG) provides neuroprotection to the injured central and peripheral nervous system. These effects may be due to regulation of myelin synthesis in glial cells and also to direct actions on neuronal function. Both types of cells express classical intracellular PROG receptors (PR), while neurons additionally express the PROG membrane-binding site called 25-Dx. In motoneurons from rats with spinal cord injury (SCI), PROG restores to normal the deficient levels of choline acetyl-transferase and of alpha3 subunit Na,K-ATPase mRNA, while levels of the growth associated protein GAP-43 mRNA are further stimulated. Recent studies suggest that neurotrophins are possible mediators of hormone action, and in agreement with this assumption, PROG treatment of rats with SCI increases the expression of brain-derived neurotrophic factor (BDNF) at both the mRNA and protein levels in ventral horn motoneurons. In situ hybridization (ISH) has shown that SCI reduces BDNF mRNA levels by 50% in spinal motoneurons, while PROG administration to injured rats (4mg/kg/day during 3 days, s.c.) elicits a three-fold increase in grain density. In addition to enhancement of mRNA levels, PROG increases BDNF immunoreactivity in perikaryon and cell processes of motoneurons of the lesioned spinal cord, and also prevents the lesion-induced chromatolytic degeneration of spinal cord motoneurons as determined by Nissl staining. Our findings strongly indicate that motoneurons of the spinal cord are targets of PROG, as confirmed by the expression of PR and the regulation of molecular parameters. PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection. Thus, PROG treatment constitutes a new approach to sustain neuronal function after injury.     

Neuropathic Pain in Rats with a Partial Sciatic Nerve Ligation Is Alleviated by Intravenous Injection of Monoclonal Antibody to High Mobility Group Box-1

High mobility group box-1 (HMGB1) is associated with the pathogenesis of inflammatory diseases. A previous study reported that intravenous injection of anti-HMGB1 monoclonal antibody significantly attenuated brain edema in a rat model of stroke, possibly by attenuating glial activation. Peripheral nerve injury leads to increased activity of glia in the spinal cord dorsal horn. Thus, it is possible that the anti-HMGB1 antibody could also be efficacious in attenuating peripheral nerve injury-induced pain. Following partial sciatic nerve ligation (PSNL), rats were treated with either anti-HMGB1 or control IgG. Intravenous treatment with anti-HMGB1 monoclonal antibody (2 mg/kg) significantly ameliorated PSNL-induced hind paw tactile hypersensitivity at 7, 14 and 21 days, but not 3 days, after ligation, whereas control IgG had no effect on tactile hypersensitivity. The expression of HMGB1 protein in the spinal dorsal horn was significantly increased 7, 14 and 21 days after PSNL; the efficacy of the anti-HMGB1 antibody is likely related to the presence of HMGB1 protein. Also, the injury-induced translocation of HMGB1 from the nucleus to the cytosol occurred mainly in dorsal horn neurons and not in astrocytes and microglia, indicating a neuronal source of HMGB1. Markers of astrocyte (glial fibrillary acidic protein (GFAP)), microglia (ionized calcium binding adaptor molecule 1 (Iba1)) and spinal neuron (cFos) activity were greatly increased in the ipsilateral dorsal horn side compared to the sham-operated side 21 days after PSNL. Anti-HMGB1 monoclonal antibody treatment significantly decreased the injury-induced expression of cFos and Iba1, but not GFAP. The results demonstrate that nerve injury evokes the synthesis and release of HMGB1 from spinal neurons, facilitating the activity of both microglia and neurons, which in turn leads to symptoms of neuropathic pain. Thus, the targeting of HMGB1 could be a useful therapeutic strategy in the treatment of chronic pain.     

The motor nuclei of the glossopharyngeal-vagal and the accessorius nerves in the rat

Retrograde cobalt labeling was performed by incubating the rootlets of cranial nerves IX, X and XI, or the central stumps of the same nerves, in a cobaltic lysine complex solution, and the distribution of efferent neurons sending their axons into these nerves was investigated in serial sections of the medulla and the cervical spinal cord in young rats. The following neuron groups were identified. The inferior salivatory nucleus lies in the dorsal part of the tegmentum at the rostral part of facial nucleus. It consists of a group of medium-sized and a group of small neurons. Their axons make a hair-pin loop at the midline and join the glossopharyngeal nerve. The dorsal motor nucleus of the vagus situates in the dorsomedial part of the tegmentum. Its rostral tip coincides with the first appearance of sensory fibres of the glossopharyngeal nerve, the caudal end extends into the pyramidal decussation. The constituting cells have globular or fusiform perikarya and they are the smallest known efferent neurons. The ambiguous nucleus is in the ventrolateral part of the tegmentum. The rostral tip lies dorsal to the facial nucleus, and the caudal tip extends to the level of the pyramidal decussation. The rostral one third of the ambiguous nucleus is composed of tightly-packed medium sized neurons, while larger neurons are arranged more diffusely in the caudal two thirds. The long dendrites are predominantly oriented in the dorsoventral direction. The dorsally-oriented axons take a ventral bend anywhere between the ambiguous nucleus and dorsal motor nucleus of the vagus. The motoneurons of the accessorius nerve are arranged in a medial, a lateral and a weak ventral cell column. The medial column begins at the caudal aspect of the pyramidal decussation and terminates in C2 spinal cord segment. The lateral and ventral columns begin in C2 segment and extend into C6 segment. The neurons have large polygonal perikarya and characteristic cross-shaped dendritic arborizations. The axons follow a dorsally-arched pathway between the ventral and dorsal horns. The accessorius motoneurons have no positional relation to any of the vagal efferent neurons. It is concluded that the topography and neuronal morphology of accessorius motoneurons do not warrant the designation of a bulbar accessorius nucleus and a bulbar accessorius nerve.     

Migration patterns of sympathetic preganglionic neurons in embryonic rat spinal cord.

The displacement of immature neurons from their place of origin in the germinal epithelium toward their adult positions in the nervous system appears to involve migratory pathways or guides. While the importance of radial glial fibers in this process has long been recognized, data from recent investigations have suggested that other mechanisms might also play a role in directing the movement of young neurons. We have labeled autonomic preganglionic cells by microinjections of horseradish peroxidase (HRP) into the sympathetic chain ganglia of embryonic rats in order to study the migration and differentiation of these spinal cord neurons. Our results, in conjunction with previous observations, suggest that the migration pattern of preganglionic neurons can be divided into three distinct phases. In the first phase, the autonomic motor neurons arise in the ventral ventricular zone and migrate radially into the ventral horn of the developing spinal cord, where, together with somatic motor neurons, they form a single, primitive motor column (Phelps P. E., Barber R. P., and Vaughn J. E. (1991). J. Comp. Neurol. 307:77-86). During the second phase, the autonomic motor neurons separate from the somatic motor neurons and are displaced dorsally toward the intermediate spinal cord. When the preganglionic neurons reach the intermediolateral (IML) region, they become progressively more multipolar, and many of them undergo a change in alignment, from a dorsoventral to a mediolateral orientation. In the third phase of autonomic motor neuron development, some of these cells are displaced medially, and occupy sites between the IML and central canal. The primary and tertiary movements of the preganglionic neurons are in alignment with radial glial processes in the embryonic spinal cord, an arrangement that is consistent with a hypothesis that glial elements might guide autonomic motor neurons during these periods of development. In contrast, during the second phase, the dorsal translocation of preganglionic neurons occurs in an orientation perpendicular to radial glial fibers, indicating that glial elements are not involved in the secondary migration of these cells. The results of previous investigations have provided evidence that, in addition to glial processes, axonal pathways might provide a substrate for neuronal migration. Logically, therefore, it is possible that the secondary dorsolateral translocation of autonomic preganglionic neurons could be directed along early forming circumferential axons of spinal association interneurons, and this hypothesis is supported by the fact that such fibers are appropriately arrayed in both developmental time and space to guide this movement.     

Two modes of cell migration in the ventral horn of the spinal cord in the chick embryo. A Golgi study

The migration process of the ventral horn in chick embryo spinal cord cells has been studied between 2.5 and 5 days of incubation (HH-17, HH-26), using the Golgi technique. Two different migratory modes are observed. Type I--Migration by nucleus translocation. Most of the ventral horn motor neurons migrate by nucleus translocation within the peripheral cylinder of the cytoplasm (migration by nucleus translocation). Type II--Free migration cells. Other cells migrate disconnected from both limiting surfaces (ventricular and pial). On the basis of shape and migratory behaviour they have been identified as smooth cells and multipodial cells.     

ErbB transmembrane tyrosine kinase receptors are expressed by sensory and motor neurons projecting into sciatic nerve.

Adult spinal cord motor and dorsal root ganglion (DRG) sensory neurons express multiple neuregulin-1 (NRG-1) isoforms that act as axon-associated factors promoting neuromuscular junction formation and Schwann cell proliferation and differentiation. NRG-1 isoforms are also expressed by muscle and Schwann cells, suggesting that motor and sensory neurons are themselves acted on by NRG-1 isoforms produced by their peripheral targets. To test this hypothesis, we examined the expression of the NRG-1 receptor subunits erbB2, erbB3, and erbB4 in rat lumbar DRG and spinal cord. All three erbB receptors are expressed in these tissues. Sciatic nerve transection, an injury that induces Schwann cell expression of NRG-1, alters erbB expression in DRG and cord. Virtually all DRG neurons are erbB2- and erbB3-immunoreactive, with erbB4 also detectable in many neurons. In spinal cord white matter, erbB2 and erbB4 antibodies produce dense punctate staining, whereas the erbB3 antibody primarily labels glial cell bodies. Spinal cord dorsal and ventral horn neurons, including alpha-motor neurons, exhibit erbB2, erbB3, and erbB4 immunoreactivity. Spinal cord ventral horn also contains a population of small erbB3+/S100beta+/GFAP- cells (GFAP-negative astrocytes or oligodendrocytes). We conclude that sensory and motor neurons projecting into sciatic nerve express multiple erbB receptors and are potentially NRG-1 responsive.