Monoaminergic Establishment of Rostrocaudal Gradients of Rhythmicity in the Neonatal Mouse Spinal Cord

2005 ◽  
Vol 94 (2) ◽  
pp. 1554-1564 ◽  
Author(s):  
Kimberly J. Christie ◽  
Patrick J. Whelan
Keyword(s):  
Spinal Cord ◽  
Locomotor Activity ◽  
Spinal Cord Injuries ◽  
Neonatal Mouse ◽  
Network Activity ◽  
Neonatal Rats ◽  
Mouse Spinal Cord ◽  
Bath Application ◽  
Rats And Mice ◽  
Calcium Green

Bath application of monoamines is a potent method for evoking locomotor activity in neonatal rats and mice. Monoamines also promote functional recovery in adult animals with spinal cord injuries by activating spinal cord networks. However, the mechanisms of their actions on spinal networks are largely unknown. In this study, we tested the hypothesis that monoamines establish rostrocaudal gradients of rhythmicity in the thoracolumbar spinal cord. Isolated neonatal mouse spinal cord preparations (P0–P2) were used. To assay excitability of networks by monoamines, we evoked a disinhibited rhythm by bath application of picrotoxin and strychnine and recorded neurograms from several thoracolumbar ventral roots. We first established that rostral and caudal segments of the thoracolumbar spinal cord had equal excitability by completely transecting preparations at the L3 segmental level and recording the frequency of the disinhibited rhythm from both segments. Next we established that a majority of ventral interneurons retrogradely labeled by calcium green dextran were active during network activity. We then bath applied combinations of monoaminergic agonists [5-HT and dopamine (DA)] known to elicit locomotor activity. Our results show that monoamines establish rostrocaudal gradients of rhythmicity in the thoracolumbar spinal cord. This may be one mechanism by which combinations of monoaminergic compounds normally stably activate locomotor networks.

Dopamine exerts activation-dependent modulation of spinal locomotor circuits in the neonatal mouse

2012 ◽  
Vol 108 (12) ◽  
pp. 3370-3381 ◽  
Author(s):  
Jennifer M. Humphreys ◽  
Patrick J. Whelan
Keyword(s):  
Spinal Cord ◽  
Feedback Loops ◽  
Ventral Root ◽  
Neonatal Mouse ◽  
Network Activity ◽  
Mouse Spinal Cord ◽  
Network Function ◽  
Renshaw Cell ◽  
Root Stimulation ◽  
Excitatory Drive

Monoamines can modulate the output of a variety of invertebrate and vertebrate networks, including the spinal cord networks that control walking. Here we examined the multiple changes in the output of locomotor networks induced by dopamine (DA). We found that DA can depress the activation of locomotor networks in the neonatal mouse spinal cord following ventral root stimulation. By examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we found that DA depresses a putative recurrent excitatory pathway that projects onto rhythm-generating circuitry of the spinal cord. This depression was D2 but not D1 receptor dependent and was not due exclusively to depression of excitatory drive to motoneurons. Furthermore, the depression in excitation was not dependent on network activity. We next compared the modulatory effects of DA on network function by focusing on a serotonin and a N-methyl-dl-aspartate-evoked rhythm. In contrast to the depressive effects on a ventral root-evoked rhythm, we found that DA stabilized a drug-evoked rhythm, reduced the frequency of bursting, and increased amplitude. Overall, these data demonstrate that DA can potentiate network activity while at the same time reducing the gain of recurrent excitatory feedback loops from motoneurons onto the network.

scholarly journals Excitatory Actions of Ventral Root Stimulation During Network Activity Generated by the Disinhibited Neonatal Mouse Spinal Cord

2009 ◽  
Vol 101 (6) ◽  
pp. 2995-3011 ◽  
Author(s):  
Agnes Bonnot ◽  
Nikolai Chub ◽  
Avinash Pujala ◽  
Michael J. O'Donovan
Keyword(s):  
Spinal Cord ◽  
Optical Activity ◽  
Metabotropic Glutamate Receptors ◽  
Ventral Root ◽  
Neonatal Mouse ◽  
Network Activity ◽  
Cholinergic Antagonists ◽  
Type I ◽  
Mouse Spinal Cord ◽  
Spinal Network

To further understand the excitatory effects of motoneurons on spinal network function, we investigated the entrainment of disinhibited rhythms by ventral root (VR) stimulation in the neonatal mouse spinal cord. A brief train of stimuli applied to a VR triggered bursting reliably in 31/32 experiments. The same roots that entrained disinhibited bursting could also produce locomotor-like activity with a similar probability when the network was not disinhibited. The ability of VR stimulation to entrain the rhythm persisted in nicotinic and muscarinic cholinergic antagonists but was blocked by the AMPAR antagonist NBQX. Bath application of the type I mGluR1 receptor antagonist CPCCOEt reduced the ability of both dorsal root and VR stimulation to entrain the disinhibited rhythm and abolished the ability of either type of stimulation to evoke locomotor-like activity. Calcium imaging through the lateral aspect of the cord revealed that VR stimulation and spontaneously occurring bursts were accompanied by a wave of activity that originated ventrally and propagated dorsally. Imaging the cut transverse face of L5 revealed that the earliest VR-evoked optical activity began ventrolaterally. The optical activity accompanying spontaneous bursts could originate ventrolaterally, ventromedially, or throughout the mediolateral extent of the ventral horn or very occasionally dorsally. Collectively, our data indicate that VR stimulation can entrain disinhibited spinal network activity and trigger locomotor-like activity through a mechanism dependent on activation of both ionotropic and metabotropic glutamate receptors. The effects of entrainment appear to be mediated by a ventrolaterally located network that is also active during spontaneously occurring bursts.

NMDA Receptor-Dependent Periodic Oscillations in Cultured Spinal Cord Networks

2001 ◽  
Vol 86 (6) ◽  
pp. 3030-3042 ◽  
Author(s):  
Edward W. Keefer ◽  
Alexandra Gramowski ◽  
Guenter W. Gross
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Rhythmic Activity ◽  
Network Size ◽  
Observation Time ◽  
Network Activity ◽  
Early Postnatal Development ◽  
Bath Application ◽  
Coefficients Of Variation ◽  
Burst Patterns

Cultured spinal cord networks grown on microelectrode arrays display complex patterns of spontaneous burst and spike activity. During disinhibition with bicuculline and strychnine, synchronized burst patterns routinely emerge. However, the variability of both intra- and interculture burst periods and durations are typically large under these conditions. As a further step in simplification of synaptic interactions, we blocked excitatory AMPA synapses with 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzoquinoxaline-7-sulphonamide (NBQX), resulting in network activity mediated through the N-methyl-d-aspartate (NMDA) receptor (NMDAONLY). This activity was APV sensitive. The oscillation under NMDAONLY conditions at 37°C was characterized by a period of 2.9 ± 0.3 s (16 separate cultures). More than 98% of all neurons recorded participated in this highly rhythmic activity. The temporal coefficients of variation, reflecting the rhythmic nature of the oscillation, were 3.7, 4.7, and 4.9% for burst rate, burst duration, and interburst interval, respectively [mean coefficients of variation (CVs) for 16 cultures]. The oscillation persisted for at least 12 h without change (maximum observation time). Once established, it was not perturbed by agents that block mGlu receptors, GABABreceptors, cholinergic receptors, purinergic receptors, tachykinin receptors, serotonin (5-HT) receptors, dopamine receptors, electrical synapses, burst afterhyperpolarization, NMDA receptor desensitization, or the hyperpolarization-activated current. However, the oscillation was destroyed by bath application of NMDA (20–50 μM). These results suggest a presynaptic mechanism underlying this periodic rhythm that is solely dependent on the NMDA synapse. When the AMPA/kainate synapse was the sole driving force ( n = 6), the resulting burst patterns showed much higher variability and did not develop the highly periodic, synchronized nature of the NMDAONLYactivity. Network size or age did not appear to influence the reliability of expression of the NMDAONLYactivity pattern. For this reason, we suggest that the NMDAONLY condition unmasks a fundamental rhythmogenic mechanism of possible functional importance during periods of NMDA receptor-dominated activity, such as embryonic and early postnatal development.

scholarly journals Orexinergic Modulation of Spinal Motor Activity in the Neonatal Mouse Spinal Cord

eNeuro ◽  
2018 ◽  
Vol 5 (5) ◽  
pp. ENEURO.0226-18.2018 ◽  
Author(s):  
Sukanya Biswabharati ◽  
Céline Jean-Xavier ◽  
Shane E. A. Eaton ◽  
Adam P. Lognon ◽  
Rhiannon Brett ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Activity ◽  
Neonatal Mouse ◽  
Mouse Spinal Cord ◽  
Spinal Motor ◽  
Spinal Motor Activity

Spike Coding During Locomotor Network Activity in Ventrally Located Neurons in the Isolated Spinal Cord From Neonatal Rat

2000 ◽  
Vol 83 (5) ◽  
pp. 2825-2834 ◽  
Author(s):  
Morten Raastad ◽  
Ole Kiehn
Keyword(s):  
Spinal Cord ◽  
Locomotor Activity ◽  
Spike Trains ◽  
Neonatal Rat ◽  
Network Activity ◽  
Lumbar Spinal Cord ◽  
Patch Clamp Technique ◽  
Important Distinction ◽  
Spike Coding ◽  
The Individual

To characterize spike coding in spinal neurons during rhythmic locomotor activity, we recorded from individual cells in the lumbar spinal cord of neonatal rats by using the on-cell patch-clamp technique. Locomotor activity was induced by N-methyl-d aspartate (NMDA) and 5-hydroxytryptamine (5-HT) and monitored by ventral root recording. We made an estimator based on the assumption that the number of spikes arriving during two halves of the locomotor cycle could be a code used by the neuronal network to distinguish between the halves. This estimator, termed the spike contrast, was calculated as the difference between the number of spikes in the most and least active half of an average cycle. The root activity defined the individual cycles and the positions of the spikes were calculated relative to these cycles. By comparing the average spike contrast to the spike contrast in noncyclic, randomized spike trains we found that approximately one half the cells (19 of 42) contained a significant spike contrast, averaging 1.25 ± 0.23 (SE) spikes/cycle. The distribution of spike contrasts in the total population of cells was exponential, showing that weak modulation was more typical than strong modulation. To investigate if this low spike contrast was misleading because a higher spike contrast averaged out by occurring at different positions in the individual cycles we compared the spike contrast obtained from the average cycle to its maximal value in the individual cycles. The value was larger (3.13 ± 0.25 spikes) than the spike contrast in the average cycle but not larger than the spike contrast in the individual cycles of a random, noncyclic spike trains (3.21 ± 0.21 spikes). This result suggested that the important distinction between cyclic and noncyclic cells was only the repeated cycle position of the spike contrast and not its magnitude. Low spike frequencies (5.2 ± 0.82 spikes/cycle, that were on average 3.5 s long) and a minimal spike interval of 100–200 ms limited the spike contrast. The standard deviation (SD) of the spike contrast in the individual neurons was similar to the average spike contrasts and was probably stochastic because the SDs of the simulated, noncyclic spike trains were also similar. In conclusion we find a highly distributed and variable locomotor related cyclic signal that is represented in the individual neurons by very few spikes and that becomes significant only because the spike contrast is repeated at a preferred phase of the locomotor cycle.

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