Rostrocaudal Progression in the Development of Periodic Spontaneous Activity in Fetal Rat Spinal Motor Circuits In Vitro

1999 ◽  
Vol 81 (5) ◽  
pp. 2592-2595 ◽  
Author(s):  
Kiyomi Nakayama ◽  
Hiroshi Nishimaru ◽  
Makito Iizuka ◽  
Shigeru Ozaki ◽  
Norio Kudo

Rostrocaudal progression in the development of periodic spontaneous activity in fetal rat spinal motor circuits in vitro. Developmental changes in the periodic spontaneous bursts in cervical and lumbar ventral roots (VRs) were investigated using isolated spinal cord preparations obtained from rat fetuses at embryonic days ( E) 13.5–18.5. Spontaneous bursts were observed in the cervical VR at E13.5–17.5, and in the lumbar VR at E14.5–17.5. Bursts occurrence in the cervical and lumbar VRs was correlated in a 1:1 fashion at E14.5–16.5. The bursts in the cervical VR preceded those in the lumbar VR at E14.5, but the latter came to precede the former by E16.5. The interval between spontaneous bursts in the lumbar VR was greatly prolonged after spinal cord transection at the midthoracic level at E14.5, whereas that in the cervical VR became significantly longer at E14.5–16.5. These results suggest that the dominant neuronal circuit initiating the spontaneous bursts shifts from cervical to lumbar region during this period. Bath application of a glutamate receptor antagonist, kynurenate (4 mM), had little effect on the spontaneous bursts in either cervical or lumbar VRs at E14.5–15.5. At E16.5, kynurenate abolished the spontaneous bursts in the cervical VR. Concomitant application of kynurenate and strychnine (5 μM), a glycine receptor antagonist, abolished all spontaneous bursts, suggesting that the major transmitter mediating the spontaneous bursts changes from glycine to glutamate in the cervical region by E16.5, but not in the lumbar region during this period.

1999 ◽  
Vol 816 (2) ◽  
pp. 493-499 ◽  
Author(s):  
Zhiyu Jiang ◽  
Kevin P Carlin ◽  
Robert M Brownstone

Author(s):  
Chunquan Cai ◽  
Changhong Shen ◽  
Weidong Yang ◽  
Qingjiang Zhang ◽  
Xiaoli Hu

Background:Neurenteric cysts are rare congenital epithelium-lined cysts of the central nervous system. They are found predominantly in the spinal cord, with lower incidence in the intracranial compartment, and may be associated with various other congenital spinal anomalies. Seven patients with symptomatic intraspinal neurenteric cysts are presented.Materials and Methods:Seven patients with intraspinal neurenteric cysts aged from nine months to ten years treated at this hospital from May 2000 to July 2006 were reviewed. The clinical manifestations, imaging and surgical findings of patients were analyzed retrospectively. All patients underwent operation. One patient's cervical neurenteric cyst was resected using the lateral cervical approach, and the other six resections were performed with posterior approach.Results:All seven patients presented with neurological involvement. One patient had an intramedullary cyst, while the other six cysts were situated ventrally. Three patients' cysts occurred in the cervical region, two in the cervicothoracic region, one in the thoracic region and one in the lumbar region. One patient had bony anomalies, and one had a lumbar posterior occult spinal dysraphism. Five patients' symptoms improved rapidly after surgery.Conclusions:Intraspinal neurenteric cysts in children are rare and most occur ventral to the spinal cord. Magnetic resonance imaging (MRI) is the most effective imaging modality. Earlier diagnosis and surgical resection of spinal neurenteric cysts improves prognosis.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
D. Krishnan ◽  
S. Viswanathan ◽  
N. Rose ◽  
H. S. N. Benjamin ◽  
A. M. Ong ◽  
...  

Abstract Background Spinal AVF (SAVF), a potentially treatable cause of myelopathy, remains a challenging diagnosis. Its rarity and non-specific imaging findings often result in misdiagnosis despite a high index of clinical suspicion. The classically described high T2 signal in the spinal cord or prominent vascular flow voids in the intradural space were not infrequently missed on initial imaging, only to be picked up at follow-up imaging after progression of symptoms. Additionally, small sized fistulas(< 1 mm) and SAVF involving less frequent locations like the craniocervical junction in a patient presenting with paraplegia further complicates the diagnosis. On rare occasions, acute atypical presentation following a surgery adds to the conundrum. Definite diagnosis with spinal angiography, the gold-standard modality requires the expertise of highly skilled interventionists which may otherwise lead to false negative findings. We describe four SAVF patients with unconventional presentations, highlighting less described clinical findings. Case presentation First was a 50-year-old man presented with spastic paraparesis and was found to have an AVF at the cervical region arising from the vertebral artery. Second, a 45-year-old man with acute paraplegia post-operatively, initially treated for a transverse myelitis before lumbar region AVF was detected. Thirdly, a 27-year-old man presented with subacute lower thoracic myelopathy and deteriorated after corticosteroid treatment. The last patient, who initially appeared to have conus medullaris/cauda equina syndrome had a SAVF at the mid thoracic level. Presentation varied with some exhibiting acute deterioration mimicking other spinal cord pathology such as inflammatory disorders. All patients eventually underwent endovascular treatment with successful embolization of SDAVF. None of them exhibited further neurological deterioration after embolization. Conclusion Successful treatment of SAVF is possible provided the diagnosis is made early, allowing timely intervention. Certain clues may aid the diagnosis. Firstly, arteriovenous fistula can be located distant to the clinical localization of myelopathy resulting in the unexpected longitudinally extensive spinal cord signal change. This clinical-radiological discrepancy can be a useful clue in diagnosing SAVF. Secondly, an acute myelopathic presentation immediately post-surgery may be related to SAVF. Other SAVF feature of note includes progressive myelopathy mimicking immune-mediated myelitis among young adults below 30 years of age refractory to immune therapy.


2021 ◽  
Vol 15 ◽  
Author(s):  
Mingchen C. Jiang ◽  
Derin V. Birch ◽  
Charles J. Heckman ◽  
Vicki M. Tysseling

Spinal cord injury (SCI) results in not only the loss of voluntary muscle control, but also in the presence of involuntary movement or spasms. These spasms post-SCI involve hyperexcitability in the spinal motor system. Hyperactive motor commands post SCI result from enhanced excitatory postsynaptic potentials (EPSPs) and persistent inward currents in voltage-gated L-type calcium channels (LTCCs), which are reflected in evoked root reflexes with different timings. To further understand the contributions of these cellular mechanisms and to explore the involvement of LTCC subtypes in SCI-induced hyperexcitability, we measured root reflexes with ventral root recordings and motoneuron activities with intracellular recordings in an in vitro preparation using a mouse model of chronic SCI (cSCI). Specifically, we explored the effects of 1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6-(1H,3H,5H)-trione (CPT), a selective negative allosteric modulator of CaV1.3 LTCCs. Our results suggest a hyperexcitability in the spinal motor system in these SCI mice. Bath application of CPT displayed slow onset but dose-dependent inhibition of the root reflexes with the strongest effect on LLRs. However, the inhibitory effect of CPT is less potent in cSCI mice than in acute SCI (aSCI) mice, suggesting changes either in composition of CaV1.3 or other cellular mechanisms in cSCI mice. For intracellular recordings, the intrinsic plateau potentials, was observed in more motoneurons in cSCI mice than in aSCI mice. CPT inhibited the plateau potentials and reduced motoneuron firings evoked by intracellular current injection. These results suggest that the LLR is an important target and that CPT has potential in the therapy of SCI-induced muscle spasms.


1997 ◽  
Vol 77 (6) ◽  
pp. 3157-3167 ◽  
Author(s):  
E. Bracci ◽  
M. Beato ◽  
A. Nistri

Bracci, E., M. Beato, and A. Nistri. Afferent inputs modulate the activity of a rhythmic burst generator in the rat disinhibited spinal cord in vitro. J. Neurophysiol. 77: 3157–3167, 1997. Application of strychnine and bicuculline to the isolated spinal cord of the neonatal rat induces spontaneous bursting of regular rhythmicity (cycle period ∼30 s). This phenomenon is important because it shows that a spinal network, made up by excitatory connections only, generates a very reliable rhythmic pattern. To find out how signals from the periphery or higher centres might influence the operation of the rhythmogenic network, the present experiments examined whether synaptic inputs from dorsal root (DR) or ventrolateral (VL) afferent fibers could modulate this spontaneous rhythmicity. This issue was addressed with intracellular recording from motoneurons or extracellular recording from ventral roots after eliciting bursting with strychnine plus bicuculline. Single electrical shocks (0.1 ms; intensity 1–4 times threshold) applied to one DR reset spontaneous bursting without altering its period or duration. Repetitive stimulations at periods ranging from 20 to 2 s entrained bursts on a 1:1 basis. Burst duration was shorter at lower stimulation periods whereas burst amplitude was unchanged. The lowest stimulation period compatible with burst entrainment depended on stimulus strength. At stimulation periods <2-s entrainment was always lost and spontaneous bursts unexpectedly returned even if electrical pulses still elicited ventral root reflexes. Such spontaneous bursts had similar properties as those recorded in the absence of electrical pulses. Analogous results were obtained with VL stimulations. It is concluded that the spinal rhythmogenic network was highly susceptible to external synaptic inputs, which paced burst generation whereas burst duration was adapted to interstimulus interval. A scheme is provided to explain the modulatory role of synaptic inputs as well as the escape of bursting from fast stimulus entrainment in terms of a rhythmogenic network functionally separated from reflex pathways activated by DR or VL tracts.


1981 ◽  
Vol 103 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Tin-Kan Hung ◽  
Guan-Liang Chang

An in-vivo experimental method was developed to measure the stress-strain relationship of a spinal cord segment of anesthetized puppies. A pseudo Young’s modulus was defined for the linear region followed by a nonlinear rheological behavior for finite strain. Both the sensory response and motor function of the puppies were fully recovered within 5 days after the spinal cord segment in the first lumbar region was elongated once by 50 percent or less. The usefulness of the in-vivo experiments was further elaborated by demonstrating the large artifacts that could be associated in an in-vitro experiment.


2020 ◽  
Author(s):  
Simon A. Sharples ◽  
Alex Vargas ◽  
Adam P. Lognon ◽  
Leanne Young ◽  
Anchita Shonak ◽  
...  

AbstractDeveloping spinal motor networks produce a diverse array of outputs, including episodic and continuous patterns of rhythmic activity. Variation in excitability state and neuromodulatory tone can facilitate transitions between episodic and continuous rhythms; however, the intrinsic mechanisms that govern these rhythms and transitions are poorly understood. Here, we tested the capacity of a single central pattern generator (CPG) circuit with tunable properties to generate multiple outputs. To address this, we deployed a computational model composed of an inhibitory half-centre oscillator. We tested the contributions of key properties predicted by the model to the generation of an episodic rhythm produced by isolated spinal cords of the newborn mouse. The model was capable of reproducing the diverse state-dependent rhythms evoked by dopamine in the neonatal mouse spinal cord. In the model, episodic bursting depended predominantly on the endogenous oscillatory properties of neurons, with persistent Na+(INaP), Na+-K+ ATPase pump (IPump), and hyperpolarization-activated currents (Ih) playing key roles. Modulation of all three currents produced transitions between episodic and continuous rhythms and silence. Pharmacological manipulation of these properties in vitro led to consistent changes in spinally generated rhythmic outputs elicited by dopamine. The model also showed multistable zones within a narrow range of parameter space for IPump and Ih, where switches between rhythms were rapidly triggered by brief but specific perturbations. Outside of those zones, brief perturbations could reset episodic and continuous rhythmicity generated by the model. Our modelling and experimental results provide insight into mechanisms that govern the generation of multiple patterns of rhythmicity by a single CPG. We propose that neuromodulators alter circuit properties to position the network within regions of state-space that favour stable outputs or, in the case of multistable zones, facilitate rapid transitions between states.Significance statementThe ability of a single CPG to produce and transition between multiple rhythmic patterns of activity is poorly understood. We deployed a complementary computational half-centre oscillator model and an isolated spinal cord experimental model to identify key currents whose interaction produced episodic and continuous rhythmic activity. Combined, our experimental and modelling approaches suggest mechanisms that govern generating and transitioning between diverse rhythms in mammalian spinal networks. This work sheds light on the ability of a single CPG to produce episodic bouts often observed in behavioural contexts.


2019 ◽  
Author(s):  
Simon A. Sharples ◽  
Nicole E. Burma ◽  
Joanna Borowska-Fielding ◽  
Charlie H.T. Kwok ◽  
Shane E.A. Eaton ◽  
...  

AbstractDopamine is well known to regulate movement through the differential control of direct and indirect pathways in the striatum that express D1 and D2 receptors respectively. The spinal cord also expresses all dopamine receptors however; how the specific receptors regulate spinal network output in mammals is poorly understood. We explore the receptor-specific mechanisms that underlie dopaminergic control of spinal network output of neonatal mice during changes in spinal network excitability. During spontaneous activity, which is a characteristic of developing spinal networks operating in a low excitability state, we found that dopamine is primarily inhibitory. We uncover an excitatory D1-mediated effect of dopamine on motoneurons and network output that also involves co-activation with D2 receptors. Critically, these excitatory actions require higher concentrations of dopamine; however, analysis of dopamine concentrations of neonates indicates that endogenous levels of spinal dopamine are low. Because endogenous levels of spinal dopamine are low, this excitatory dopaminergic pathway is likely physiologically-silent at this stage in development. In contrast, the inhibitory effect of dopamine, at low physiological concentrations is mediated by parallel activation of D2, D3, D4 and α2 receptors which is reproduced when endogenous dopamine levels are increased by blocking dopamine reuptake and metabolism. We provide evidence in support of dedicated spinal network components that are controlled by excitatory D1 and inhibitory D2 receptors that is reminiscent of the classic dopaminergic indirect and direct pathway within the striatum. These results indicate that network state is an important factor that dictates receptor-specific and therefore dose-dependent control of neuromodulators on spinal network output and advances our understanding of how neuromodulators regulate neural networks under dynamically changing excitability.Significance statementMonoaminergic neuromodulation of neural networks is dependent not only on target receptors but also on network state. We studied the concentration-dependent control of spinal networks of the neonatal mouse, in vitro, during a low excitability state characterized by spontaneous network activity. Spontaneous activity is an essential element for the development of networks. Under these conditions, we defined converging receptor and cellular mechanisms that contribute to the diverse, concentration-dependent control of spinal motor networks by dopamine, in vitro. These experiments advance understanding of how monoamines modulate neuronal networks under dynamically changing excitability conditions and provide evidence of dedicated D1 and D2 regulated network components in the spinal cord that are consistent with those reported in the striatum.


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