Contralaterally projecting lamina VIII interneurones in middle lumbar segments in the cat

Peripheral input to lamina VIII interneurones was investigated by using extracellular and/or intracellular records from them. The interneurones were located in the L4-L5 spinal segments and projected to contralateral motor nuclei in the L7 segment. They constituted a non-homogeneous population but their input from muscle afferents (mainly group II afferents of quadriceps, flexor digitorum longus and pretibial flexors and group I afferents of triceps surae and hamstring nerves) and from cutaneous and joint afferents resembled the input to ipsilaterally projecting laminae V-VII interneurones of the same segments rather than the input to more caudally located lamina VIII interneurones. Since the ipsilaterally projecting laminae V-VII interneurones with such an input might be involved in locomotion, it is proposed that this is also the case for the contralaterally projecting lamina VIII midlumbar interneurones, especially those excited by stimuli applied in the cuneiform nucleus (mesencephalic locomotor region).     

Excitatory components of the mammalian locomotor CPG

Locomotion in mammals is to a large degree controlled directly by intrinsic spinal networks, called central pattern generators (CPGs). The overall function of these networks is governed by interaction between inhibitory and excitatory neurons. In the present review, we will discuss recent findings addressing the role of excitatory synaptic transmission for network function including the role of specific excitatory neuronal populations in coordinating muscle activity and in generating rhythmic activity.     

Organization of left–right coordination in the mammalian locomotor network

Neuronal circuits involved in left–right coordination are a fundamental feature of rhythmic locomotor movements. These circuits necessarily include commissural interneurons (CINs) that have axons crossing the midline of the spinal cord. The properties of CINs have been described in some detail in the spinal cords of a number of aquatic vertebrates including the Xenopus tadpole and the lamprey. However, their function in left–right coordination of limb movements in mammals is poorly understood. In this review we describe the present understanding of commissural pathways in the functioning of spinal cord central pattern generators (CPGs). The means by which reciprocal inhibition and integration of sensory information are maintained in swimming vertebrates is described, with similarities between the three basic populations of commissural interneurons highlighted. The subsequent section concentrates on recent evidence from mammalian limbed preparations and specifically the isolated spinal cord of the neonatal rat. Studies into the role of CPG elements during drug-induced locomotor-like activity have afforded a better understanding of the location of commissural pathways, such that it is now possible, using whole cell patch clamp, to record from anatomically defined CINs located in the rhythm-generating region of the lumbar segments. Initial results would suggest that the firing pattern of these neurons shows a greater diversity than that previously described in swimming central pattern generators. Spinal CINs play an important role in the generation of locomotor output. Increased knowledge as to their function in producing locomotion is likely to provide valuable insights into the spinal networks required for postural control and walking.     

Plasticity of interneuronal networks of the functionally isolated human spinal cord

The loss of walking after human spinal cord injury has been attributed to the dominance of supraspinal over spinal mechanisms. The evidence for central pattern generation in humans is limited due to the inability to conclusively isolate the circuitry from descending and afferent input. However, studying individuals following spinal cord injury with no detectable influence on spinal networks from supraspinal centers can provide insight to their interaction with afferent input. The focus of this article is on the interaction of sensory input with human spinal networks in the generation of locomotor patterns. The functionally isolated human spinal cord has the capacity to generate locomotor patterns with appropriate afferent input. Locomotor Training is a rehabilitative strategy that has evolved from animal and humans studies focused on the neural plasticity of the spinal cord and has been successful for many people with acute and chronic incomplete spinal cord injury. However, even those individuals with clinically complete spinal cord injury that generate appropriate locomotor patterns during stepping with assistance on a treadmill with body weight support cannot sustain overground walking. This suggests that although a significant control of locomotion can occur at the level of spinal interneuronal networks the level of sustainable excitability of these circuits is still compromised. Future studies should focus on approaches to increase the central state of excitability and may include neural repair strategies, pharmacological interventions or epidural stimulation in combination with Locomotor Training.     

Spinal input to the parabrachial nucleus in the cat

The projections from the spinal cord to the parabrachial nucleus in the cat were investigated using both the degeneration method and the anterograde transport of wheat germ agglutinin-horseradish peroxidase conjugate. Both methods produced similar results. Spinal input to the parabrachial nucleus was bilateral, with a slight contralateral predominance. The termination area was localized predominantly in the dorsal part of the lateral parabrachial nucleus, with additional limited terminations in the Kölliker-Fuse subnucleus. Projections from different rostrocaudal levels of the spinal cord overlapped completely, suggesting that spinal input to the parabrachial nucleus is not topographically organized. Taking these results together with those of others indicating that spinal input to the parabrachial nucleus arises primarily from nociceptive-specific neurons in lamina I of the dorsal horn, it is concluded that the spinal projections to the parabrachial nucleus are likely to be involved in various generalized aspects of nociception.     

Spinal plasticity mediated by postsynaptic L-type Ca channels

In the spinal cord, motoneurons and specific subgroups of interneurons express L-type Ca²⁺ channels. As elsewhere, these dihydropyridine-sensitive channels mediate a slowly activating inward current in response to depolarisation and show little or no inactivation. The slow kinetics for activation and deactivation provide voltage-sensitive properties in a time range from hundreds of milliseconds to tens of seconds and lead to plateau potentials, bistability and wind-up in neurons in both sensory and motor networks. This slow dynamics is in part due to facilitation of L-type Ca²⁺ channels by depolarisation. The voltage sensitivity of L-type Ca²⁺ channels is also regulated by a range of metabotropic transmitter receptors. Up-regulation is mediated by receptors for glutamate, acetylcholine, noradrenaline and serotonin in motoneurons and by receptors for glutamate and substance P in plateau-generating dorsal horn interneurons. In both cell types, L-type Ca²⁺ channels are down-regulated by activation of GABA_B receptors. In this way, metabotropic regulation in cells expressing L-type Ca²⁺ channels provides mechanisms for flexible adjustment of excitability and of the contribution of plateau currents to the intrinsic properties. This type of regulation also steers the magnitude and compartmental distribution of Ca²⁺ influx during depolarisation, thus providing a signal for local synaptic plasticity.     

Spinal intramedullary angiolipoma

We report the case of a young patient with a thoracolumbar (T11-L3) intramedullary angiolipoma. Total removal of the tumor was possible and after operation the patient's neurological condition greatly improved. Only two previous cases of intramedullary angiolipomas have been reported, and in neither could the lesion be wholly removed. The histopathological and radiological features of these tumors are discussed and the extreme rareness of this case is emphasized.     

Spinal Cord Stimulation Enhances Microglial Activation in the Spinal Cord of Nerve-Injured Rats

Microglia can modulate spinal nociceptive transmission. Yet, their role in spinal cord stimulation (SCS)-induced pain inhibition is unclear. Here, we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury (CCI) of the sciatic nerve. Male rats received conventional SCS (50 Hz, 80% motor threshold, 180 min, 2 sessions/day) or sham stimulation on days 18–20 post-CCI. SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns. SCS also upregulated the mRNAs of M1-like markers, but not M2-like markers. Inducible NOS protein expression was increased, but brain-derived neurotrophic factor was decreased after SCS. Intrathecal minocycline (1 μg–100 μg), which inhibits microglial activation, dose-dependently attenuated the mechanical hypersensitivity. Pretreatment with low-dose minocycline (1 μg, 30 min) prolonged the SCS-induced pain inhibition. These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.     

Effects of body position on crossed extension reflex in decerebrate cat: rectus femoris is more sensitive than is vastus medialis

Physiological stimuli which increase postural extensor tone also excitability of the crossed extension reflex (CER). We report here that such stimuli increase excitability of the CER recorded from rectus femoris (RF) more than that of vastus medialis (VM). The difference might reflect an important role of the biarticular actions of RF, which is also a weak hip flexor, in stabilizing the hip as well as extending the knee during maintenance of posture.     

Age-related changes in human spinal ventral horn cells with special reference to the loss of small neurons in the intermediate zone: a quantitative analysis

A cytoarchitectonic study of spinal ventral horn cells was performed to identify age-related changes. The diameter distribution of ventral horn neurons of the fourth lumbar segment of the spinal cord and their size and topographical distributions were investigated in 14 autopsy cases. These cases represented patients of 18–100 years of age who had died of non-neurological diseases. The results indicate that small neurons widely distributed in the intermediate zone of the ventral horn significantly diminished with aging (P < 0.0005, r = –0.898), whereas medium-sized and large neurons located in the medial and lateral nuclei showed only a slight decrease with advancing age. The total number of neurons in the whole ventral horn was also noted to decrease significantly with aging (P < 0.0005, r = –0.899). While small neurons in the intermediate zone of the ventral horn are thought to be mostly interneurons, their physiological function still remains obscure in many respects. The findings of this study provide insight into age-related cell loss in terms of size and location. Received: 24 November 1995 / Accepted: 26 February 1996     

Spinal cord glioblastoma: 25 years of experience from a single institution

Accounting for less than 0.2% of all glioblastomas, high grade gliomas of the spinal cord are very rare. Here, we discuss our approach to managing patients with high grade spinal cord glioma and review the literature on the subject. Six patients with high grade spinal cord gliomas who presented to our institution between 1990 and 2015 were reviewed. Each patient underwent subtotal surgical resection, with a subset receiving adjuvant chemotherapy and radiation. Our primary outcomes of interest were pre-operative and post-operative functional status. One year survival rate was 100%. All patients had stable or improved American Spine Injury Association score immediately after surgery, which was maintained at 3 months in 83.3% of patients. Karnofsky Performance Status (KPS) was stable at 3 month follow up in 50% of patients, but all had decreased KPS 1 year after surgery. A subset of patients received post-operative radiation and chemotherapy with 0% tumor recurrence rate at 3 months. We assessed the molecular profiles of tumors from two patients in our series and found that each had mutations in TP53, but had wildtype BRAF, IDH-1, and MGMT. Taken together, our data show that patients with high grade spinal cord gliomas have an excellent survival at 1 year, but with some decline in functional status within this period. Further studies are needed to elucidate the natural history of the disease and to explore the role of adjuvant targeted molecular therapies.     

Glycine-like immunoreactivity in synaptic boutons of identified inhibitory interneurons in the mammalian spinal cord

Glycine is thought ti be a major inhibitory neurotransmitter in the mammalian CNS. Two types of physiologically identified interneurons, Renshaw cells and Ia inhibitory interneurons, were intracellularly staind with horseradish peroxidase, and their axon terminals were studied at the electron microscopic level. Post-embedding immunogold procedures weer used to reveal the presence of glycine-like immunoreactivity. The synaptic terminals of both types of interneuron were significantly enriched with glycine-like immunoreactivity, providing support for the idea that glycine is a mediator of synaptic transmission in the recurrent and reciprocal inhibitory pathways to motoneurons.     

Spinal cord metabolic response to noxious radiant heat stimulation of the cat hind footpad

The 2-deoxy[¹⁴C]glucose (2-DG) method was used to study glucose utilization in the cat lumbar spinal cord during noxious thermal stimulation to the hind footpad. Spinal cord glucose utilization in stimulated cats was twice that of control animals. Diffusely increased metabolic activity was seen in the ipsilateral dorsal horn. The highest levels of 2-DG were seen in the ipsilateral ventral horn, while a moderate increase was seen in the contralateral ventral horn.     

Spinal meningioma becoming symptomatic in the third trimester of pregnancy

We report a rare case of a spinal meningioma leading to symptoms of spinal cord compression starting in the third trimester of gestation in a 32-year-old woman. Neurological symptoms, which continued to progress after the patient had given birth, were assumed to be sequelae of pregnancy and delivery, leading to a 6 month delay in diagnosis and treatment. Fortunately a gross total resection was achieved at surgery and the patient recovered fully, without permanent consequences. Associated symptoms of spinal cord compression may be falsely attributed to pregnancy, both by the pregnant women and her treating physician. A high index of suspicion and thorough history and physical examination to identify red flags should be performed in patients with neurological symptoms.     

Spinal infarcts

Compared to cerebral ischaemia, the frequency of spinal cord ischaemia is rare. Spinal infarcts lead to various types of neurological deficits, usually consisting of an abrupt and complete tetra- or paraplegia. Magnetic resonance imaging is the most valuable tool to show the infarct and to rule out other causes of acute spinal cord syndromes., such as myelitis or acute compressions. Nowadays, in western countries, most spinal cord infarcts are due to aortic diseases (atherosclerosis, aneurysm, dissection) or are of iatrogenic origin (mainly aortic surgery and interventional radiology), while other causes are rare. There is no specific treatment, besides prevention of complications, treatment of the underlying cause and rehabilitation.     

Postsynaptic dorsal column and cuneate neurons in raccoon: comparison of response properties and cross-correlation analysis

The responses of 111 postsynaptic dorsal column (PSDC) neurons in the cervical spinal cord and 51 cuneate neurons with receptive fields on the glabrous skin of the forepaw were studied in anesthetized raccoons using extracellular recording techniques. The PSDC neurons had larger receptive fields than the cuneate neurons, but in both groups the fields never extended onto hairy skin. PSDC and cuneate neurons had approximately the same mean latency to electrical stimulation of the receptive field, but PSDC neurons had significantly lower thresholds. The majority of both PSDC and cuneate neurons also responded to electrical stimulation of an adjacent digit, even though they did not respond to mechanical stimulation of that digit. Cross-correlation analysis of the activity of 51 pairs of PSDC and cuneate neurons recorded simultaneously revealed a significant interaction in 26 pairs during spontaneous activity. In 20 of these neuron pairs, the probability that the cuneate neuron would fire was greater after the PSDC neuron had fired (suggesting a spinocuneate interaction), five pairs showed an interaction in the opposite (cuneospinal) direction, and one pair had a significant inhibitory interaction. These interactions occurred more often when the receptive fields of the two neurons were overlapping than when their fields were on adjacent digits. Frequency response analysis revealed greater coherence for those pairs showing a spinocuneate interaction than for those with a cuneospinal interaction. These results support the hypothesis that the PSDC system exerts a tonic facilitatory effect on cuneate neurons and that there may be some somatotopic organization to the interactions. However, the similar response latencies of the two groups of neurons makes it unlikely that PSDC neurons could contribute to the rapid initial processing of cutaneous information by the cuneate nucleus.     

Axon branching of medullary expiratory neurons in the lumbar and the sacral spinal cord of the cat

Intraspinal axon collaterals of expiratory (E) neurons in the caudal nucleus retroambigualis extending their ascending spinal axons to the lower lumbar (L6-L7) and the sacral (S1-S3) segments were investigated in anesthetized cats. To search for axon collaterals of single E neurons in the lumbar segments, the spinal gray matter was microstimulated from the dorsal to the ventral sites at 100 μm intervals with an intensity of 150–250 μA at 1 mm intervals rostrocaudally along the spinal cord, and effective stimulating sites of antidromic activation in axon collaterals were systematically mapped. In addition, the detailed trajectory of collaterals in the upper lumbar (L1-L3), the middle lumbar (L4-L5), and the sacral (S1-S3) spinal cord was examined by microstimulation at a matrix of points 100–200 μm apart with a maximum stimulus intensity of 50 μA. The trajectory of axon collaterals was reconstructed on the basis of the location of low-threshold foci and the latency of antidromic spikes. Virtually all E neurons examined had 1–7 collaterals at widely separated segments of the lumbar cord. Many axon collaterals were found in the upper lumbar spinal cord as compared to the middle and the lower lumbar spinal cord. The locations of axon collaterals in the upper lumbar spinal cord overlapped with those of abdominal motoneurons. Axon collaterals in the sacral gray matter were found in 3 of 9 E neurons. Axon collateral were found within the nucleus of Onuf, in the region dorsal to the nucleus of Onuf, and in the intermediate region. The functional significance of the divergent distribution of multiple axon collaterals of single E neurons in different spinal levels of the lumbar and the sacral spinal cord is discussed in relation to the respiratory function of E neurons and other spinal motor activities.