Nitric oxide (NO) plays an important role in pathophysiology of the nervous system. Copper/zinc superoxide dismutase (SOD1) reacts with superoxide, which is also a substrate for NO, to provide antioxidative protection. NO production is greatly altered following nerve injury, therefore we hypothesised that SOD1 and NO may be involved in ...

Electrical synapses formed by gap junctions containing connexin36 (Cx36) promote synchronous activity of interneurones in many regions of mammalian brain, however, there is limited information on the role of electrical synapses in spinal neuronal networks. Here we show that Cx36 is widely distributed in the spinal cord and is involved ...

Bone Morphogenetic Proteins (BMPs) have multiple activities in the developing spinal cord: they specify the identity of the dorsal-most neuronal populations and then direct the trajectories of dorsal interneuron (dI) 1 commissural axons. How are these activities decoded by dorsal neurons to result in different cellular outcomes? Our previous studies ...

The sensory circuit of the stretch reflex arc is composed of intrafusal muscle fibers and their innervating proprioceptive neurons that convert mechanical information regarding muscle length and tension into action potentials that synapse onto the homonymous motoneurons in the ventral spinal cord which innervate the extrafusal fibers of the same ...

The transient suppression of motor activity in the spinal cord after a cutaneous stimulus is termed the cutaneous silent period (CSP). It is not known if CSP is due to suppression of the premotor network or direct inhibition of motoneurons. This issue was examined by intracellular recordings from motoneurons in ...

Despite the diverse methods vertebrates use for locomotion, there is evidence that components of the locomotor central pattern generator (CPG) are conserved across species. When zebrafish begin swimming early in development they perform short episodes of activity separated by periods of inactivity. Within these episodes, the trunk flexes with side-to-side ...

OBJECTIVE: To investigate the P18 component in the posterior to anterior neck montage after median nerve stimulation. METHODS: Somatosensory evoked potentials, through electrical wrist stimulation, were collected. In 12 subjects, the presence of the P18 component was evaluated in the posterior to anterior neck montage. In 10 subjects, the effects ...

Whole-cell patch-clamp electrophysiology of neurons is a gold-standard technique for high-fidelity analysis of the biophysical mechanisms of neural computation and pathology, but it requires great skill to perform. We have developed a robot that automatically performs patch clamping in vivo, algorithmically detecting cells by analyzing the temporal sequence of electrode ...

Chronic pain is thought to arise because of maladaptive changes occurring within the peripheral nervous system and CNS. The transition from acute to chronic pain is known to involve the spinal cord (Woolf and Salter, 2000). Therefore, to investigate altered human spinal cord function and translate results obtained from other ...

Epoxyeicosatrienoic acids (EETs) are cytochrome P450-epoxygenase-derived metabolites of arachidonic acid that act as endogenous signaling molecules in multiple biological systems. Here we have investigated the specific contribution of 5,6-EET to transient receptor potential (TRP) channel activation in nociceptor neurons and its consequence for nociceptive processing. We found that, during capsaicin-induced ...

Sustained inflammatory reactions are common pathological events associated with neuron loss in neurodegenerative diseases. Reported evidence suggest that Toll-like receptor 4 (TLR4) is a key player of neuroinflammation in several neurodegenerative diseases. The mechanisms by which TLR4 mediates neurotoxic signals remain however poorly understood.We investigated the role of TLR4 in ...

Functional studies have shown that subsets of autonomic preganglionic neurons respond to ghrelin and ghrelin mimetics and in situ hybridisation has revealed receptor gene expression in the cell bodies of some preganglionic neurons. Our present goal has been to determine which preganglionic neurons express ghrelin receptors by using mice expressing ...

Overactivity of poly(ADP-ribose) polymerase enzyme 1 (PARP-1) is suggested to be a major contributor to neuronal damage following brain or spinal cord injury, and has led to study the PARP-1 inhibitor 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2yl)acetamide (PJ-34) as a neuroprotective agent. Unexpectedly, electrophysiological recording from the neonatal rat spinal cord in vitro showed that, under ...

The paraventricular nucleus (PVN) of the hypothalamus has a heterogenous structure containing different types of output neurons that project to the median eminence, posterior pituitary, brain stem autonomic centers and sympathetic preganglionic neurons in the spinal cord. Presympathetic neurons in the PVN send mono- and poly-synaptic projections to the spinal ...

In the spinal cord dorsal horn, presynaptic GABA(A) receptors (GABA(A) R) in the terminals of nociceptors as well as postsynaptic receptors in spinal neurons regulate the transmission of nociceptive and somatosensory signals from the periphery. GABA(A) R are heterogeneous and distinguished functionally and pharmacologically by the type of α subunit ...

Spinal cord stimulation (SCS) inhibits substance P (SP) release and decreases the expression of the transient receptor potential vanilloid 1 (TRPV1) in the spinal cord at thoracic 4 (T4) during cardiac ischemia in rat models (Ding et al., 2007). We hypothesized that activation of TRPV1 in the T4 spinal cord ...

Establishment of proper connectivity between peripheral sensory neurons and their central targets is required for an animal to sense and respond to various external stimuli. Dorsal root ganglion (DRG) neurons convey sensory signals of different modalities via their axon projections to distinct laminae in the dorsal horn of the spinal ...

It has been reported that central chemoreceptor cells in the medulla are distributed in close apposition to capillary blood vessels in the medulla. Phox2b-expressing neurons in the retrotrapeziod nucleus (RTN) respond to high CO(2)/H(+) stimulation and have been suggested to play an important role in central chemoreception. In newbornrats, the ...

Bone marrow stromal cell (BMSC) transplantation has shown promise for repair of the spinal cord. We showed earlier that a BMSC transplant limits the loss of spinal nervous tissue after a contusive injury. Here, we addressed the premise that BMSC-mediated tissue sparing underlies functional recovery in adult rats after a ...

Coordinated limb rhythmic movements take place through organized signaling in local spinal cord neuronal networks. The establishment of these circuitries during development is dependent on the correct guidance of axons to their targets. It has previously been shown that the well-known axon guidance molecule netrin-1 is required for configuring the ...

The final motor output underlying behavior arises from an appropriate balance between excitation and inhibition within neural networks. Retrograde signaling by endocannabinoids adapts synaptic strengths and the global activity of neural networks. In the spinal cord, endocannabinoids are mobilized postsynaptically from network neurons and act retrogradely on presynaptic cannabinoid receptors ...

This study explores the ability of a catalytic antioxidant, Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), to protect against neuronal and glial oxidative stress and death after spinal cord injury (SCI). Nine different doses of MnTBAP were administered into the intrathecal space of the rat spinal cord immediately following moderate ...

The aim of the present study was to artificially induce plasticity in the human spinal cord and evaluate whether this plasticity is pathway specific. For this purpose, a technique called paired associative stimulation (PAS) was applied. Volleys evoked by transcranial magnetic stimulation over the primary motor cortex and peripheral nerve ...

Dorsal spinal cord neurons receive and integrate somatosensory information provided by neurons located in dorsal root ganglia. Here we demonstrate that dorsal spinal neurons require the Krüppel-C(2)H(2) zinc-finger transcription factor Bcl11a for terminal differentiation and morphogenesis. The disrupted differentiation of dorsal spinal neurons observed in Bcl11a mutant mice interferes with ...

Neuro-axonal damage is a major hallmark of multiple sclerosis (MS). To date, not much is known on the underlying mechanisms of neuronal degeneration. In disease model myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), there is a significant loss of alpha motorneurons in the cervical as well as thoracic and ...

The extension of axons through the major inhibitory component of the glial scar, chondroitin sulfate proteoglycans (CSPGs), remains a key obstacle for regeneration following spinal cord injury (SCI). We have previously shown that transplants composed of neuronal and glial restricted precursors (NRP and GRP respectively) promote regeneration and connectivity in ...

In contrast to mammals, adult zebrafish regenerate neurons in the the lesioned spinal cord. For example, motor neurons are generated from an olig2 expressing population of pMN-like ependymo-radial glial cells in a ventro-lateral position at the central canal. However, the extent of neuronal regeneration is unclear. Here we show, using ...

Transplantation of adipose-derived stem cells (ASCs) is one of the possible therapeutic tools for ischemic damage. In this study, we observed the effects of ASCs against ischemic damage in the ventral horn of L(5-6) levels in the rabbit spinal cord. ASCs were isolated from rabbits, and cell type was confirmed ...

Motor neurons (MNs) are designated as alpha/gamma and fast/slow based on their target sites and the types of muscle fibers innervated; however, few molecular markers that distinguish between these subtypes are available. Here we report that osteopontin (OPN) is a selective marker of alpha MNs in the mouse spinal cord. ...

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Inhibition usually decreases input-output excitability of neurons. If, however, inhibition is coupled to excitation in a push-pull fashion, where inhibition decreases as excitation increases, neuron excitability can be increased. Although the presence of push-pull organization has been demonstrated in single cells, its functional impact on neural processing depends on its ...

In vitro studies have repeatedly demonstrated that the neurotransmitters γ-aminobutyric acid (GABA) and glycine depolarize immature neurons in many areas of the central nervous system, including the spinal cord. This widely accepted phenomenon was recently challenged by experiments showing that the depolarizing action of GABA on neonatal hippocampus and neocortex ...

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize ...

Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to ...

PlexinsA1-A4 participate in class 3 semaphorin signaling as co-receptors to neuropilin 1 and 2, PlexinA4 being the latest member of the PlexinA subfamily to be identified. Little is known about the cellular distribution of PlexinA4 in the spinal cord and dorsal root ganglion (DRG). Here, immunohistochemical studies using antibodies to ...

Our understanding of the neural control of locomotion has been greatly enhanced by the ability to identify and manipulate genetically defined populations of interneurons that comprise the locomotor central pattern generator (CPG). To date, the dI6 interneurons are one of the few populations that settle in the ventral region of ...

Sensory input from the periphery to the brain can be severely compromised or completely abolished after an injury to the spinal cord. Evidence from animal models suggests that endogenous repair processes in the spinal cord mediate extensive sprouting and that this might be further attenuated by targeted therapeutic interventions. However, ...

The objective of this study was to explore changes in hyaluronan levels in the cerebrospinal fluid (CSF) in a spinal cord compression model, to investigate whether hyaluronan tetrasaccharide was involved in this process, and to test the effects of hyaluronan tetrasaccharide on neuron and oligodendrocyte repair. We developed a chronic ...

Study Design: An in vivo animal study to examine the influence of pre-existing or concurrent spinal canal stenosis (SCS) on the functional recovery after spinal cord injury (SCI).Objectives: To clarify whether spinal cord compression before or after SCI results in less favorable neurological recovery.Summary of Background Data: The influence of ...

The organization of the minimal neuronal substrate capable of generating locomotor rhythmicity in vertebrates is investigated in several species, with an emphasis on identifying evolutionary-conserved features. In lamprey, an eel-like lower vertebrate that swims by undulatory movements of the body, the network has been identified as a recurrent network of ...

In this review we will describe newly developed techniques that are being used to recover levels of motor function after a severe spinal cord injury that have not been observed previously. These new approaches include pharmacological neuromodulation and/or epidural stimulation of the spinal cord circuitries in combination with motor training. ...

An acute lesion to the spinal cord triggers complex mechanisms responsible for amplification of the initial damage and its chronicity. In vitro preparations of the rodent spinal cord retain the intrinsic ability to produce locomotor-like discharges from lumbar ventral roots and, thus, offer the opportunity to study the still unclear ...

The modern monotremes (platypus and echidnas) are characterized by development of their young in a leathery egg that is laid into a nest or abdominal pouch. At hatching, the young are externally immature, with forelimbs capable of digitopalmar prehension, but hindlimbs little advanced beyond limb buds. The embryological collections at ...

Mammalian motor circuits control voluntary movements by transmitting signals from the central nervous system (CNS) to muscle targets. To form these circuits, motor neurons (MNs) must extend their axons out of the CNS. Although exit from the CNS is an indispensable phase of motor axon pathfinding, the underlying molecular mechanisms ...

We studied the pathologic features of neurons that contain intracytoplasmic acidophilic droplets (IADs) in chicken spinal cords. The IADs were lustrous spheroid bodies scattered in the cytoplasm of neurons, variable in size, and protein-rich bodies stained eosinophilic with hematoxylin-eosin, acidophilic with Azan, blue indigo with phosphotungstic acid hematoxylin, and yellow-green ...

New developments in nanotechnology are increasingly designed to modulate relevant interactions between nanomaterials and neurons, with the aim of exploiting the physical properties of synthetic materials to tune desired and specific biological processes. Carbon nanotubes have been applied in several areas of nerve tissue engineering to study cell behavior or ...

The opioid-related receptor, ORL1, is activated by the neuropeptide nociceptin/orphanin FQ (N/OFQ) and inhibits high-voltage activated (HVA) calcium channel currents (ICa) via a G-protein coupled mechanism. Endocytosis of ORL1 receptor during prolonged N/OFQ exposure was proposed to cause N-type voltage-gated calcium channel (VGCC) internalization via physical interaction between ORL1 and ...

The cerebellum receives information from the hindlimbs through several populations of spinocerebellar tract neurons. Although the role of these neurons has been established in electrophysiological experiments, the relative contribution of afferent fibres and central neurons to their excitatory input has only been estimated approximately so far. Taking advantage of differences ...

Spinal cord development is a complex process involving generation of the appropriate number of cells, acquisition of distinctive phenotypes and establishment of functional connections that enable execution of critical functions such as sensation and locomotion. Here we review the basic cellular events occurring during spinal cord development, highlighting studies that ...

This work compares the effects of electrical stimulation of the paraventricular hypothalamic nucleus (PVN) and the raphe magnus nucleus (RMg) on the single-unit response from dorsal spinal cord neurons activated by nociceptive receptive field stimulation. We evaluated the effects of stimulating the PVN or RMg individually or simultaneously, as well ...