A reliable technique for the induction of locomotor-like activity in the in vitro neonatal rat spinal cord using brainstem electrical stimulation

Zaporozhets, Eugene; Cowley, Kristine C.; Schmidt, Brian J.

doi:10.1016/j.jneumeth.2004.04.009

Cited by 44 publications

(50 citation statements)

References 31 publications

(50 reference statements)

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“…This flexibility was shown in the present experiments by activating spinal interneuronal systems using different pathways and finding that each of the three different stimulation methods examined here evoked a distinct motor pattern. Although we have not examined this issue systematically, it would not be surprising if the rhythmic patterns evoked by other stimulation methods, such as brain stem stimulation (Zaporozhets et al 2004) or stimulation of different dorsal roots (Marchetti et al 2001) or ventral roots (Mentis et al 2005), would similarly produce patterns distinct from the ones described here. Note that brain stem stimulation evokes a pattern of muscle activations with quadcripes active mainly in extension (Zaporozhets et al 2004), which, depending on which head of quadriceps was recorded from, would make it roughly similar to the CE-evoked patterns seen here.…”

Section: Discussionmentioning

confidence: 78%

“…In addition to pharmacological activation, there are several other ways to evoke locomotor-like rhythmic patterns in this preparation. In particular, electrical stimulation of inputs to the spinal cord, either by stimulation of dorsal (Marchetti et al 2001) or ventral (Mentis et al 2005) roots, of the cauda equina (CE) (Lev-Tov et al 2000;Strauss and Lev-Tov 2003), or of descending brain stem (Zaporozhets et al 2004) pathways is commonly used to evoke rhythmic patterns. This stimulation is potentially more physiologically interpretable as compared with the bath application of pharmacological agents, relying on the synaptic connectivity of those inputs to spinal interneurons rather than the global activation of neurons by bath-applied agents.…”

Section: Introductionmentioning

confidence: 99%

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Flexibility of Motor Pattern Generation Across Stimulation Conditions by the Neonatal Rat Spinal Cord

Klein

Patino

Tresch

2010

Journal of Neurophysiology

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Klein DA, Patino A, Tresch MC. Flexibility of motor pattern generation across stimulation conditions by the neonatal rat spinal cord. J Neurophysiol 103: 1580 -1590, 2010. First published January 20, 2010 doi:10.1152/jn.00961.2009. Previous studies have demonstrated that "locomotor-like" rhythmic patterns can be evoked in the isolated neonatal rat spinal cord by several means, including pharmacological neuromodulation and electrical stimulation of various pathways. Recent studies have used stimulation of afferent pathways to evoke rhythmic patterns, relying on synaptic activation of interneuronal systems rather than global imposition of neuromodulatory state by pharmacological agents. We use the in vitro neonatal rat spinal cord with attached hindlimb to examine the muscle activation patterns evoked by stimulation of these different pathways and evaluate whether stimulation of these pathways all evoke the same patterns. We find that the patterns evoked by bath application of serotonin (5-HT) and N-methyl-D-aspartic acid (NMDA) consisted of alternation between hip flexors and extensors and similar alternation was observed in the patterns evoked by electrical stimulation of the cauda equina (CE) or contralateral fifth lumbar (L 5 ) dorsal nerve root. In contrast, the knee extensor/hip flexor rectus femoris (RF) and knee flexor/hip extensor semitendinosus (ST) were activated differentially across stimulation conditions. In 5-HT/NMDA patterns, RF was active in late flexion and ST in late extension. In CE patterns, these two muscles switched places with RF typically active in late extension and ST active in flexion. In L 5 patterns, ST was activated in extension and RF was silent or weakly active during flexion. There were also systematic differences in the consistency of rhythms evoked by each stimulation method: patterns evoked by electrical stimulation of CE or L 5 were less consistently modulated with the rhythm when compared with 5-HT/NMDA-evoked patterns. All differences were preserved following deafferentation, demonstrating that they reflect intrinsic properties of spinal systems. These results highlight the intrinsic flexibility of motor pattern generation by spinal motor circuitry which is present from birth and provides important information to many studies examining spinal pattern generating networks.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Flexibility of Motor Pattern Generation Across Stimulation Conditions by the Neonatal Rat Spinal Cord

Klein

Patino

Tresch

2010

Journal of Neurophysiology

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“…For example, blocking synaptic activity in the cervicothoracic cord suppresses lumbar locomotorrelated activity that is otherwise elicited by electrical or chemical brainstem stimulation, thereby indicating the primary involvement of propriospinal synaptic relays in mediating the descending signal transmission (Zaporozhets et al, 2004(Zaporozhets et al, , 2006. Correspondingly, brainstem-evoked activation of the lumbar CPGs is unaffected by the staggered disruption of long ipsilateral bulbospinal projections, but the propagation of locomotory command signals is facilitated by increasing neuronal excitability in the intervening cervicothoracic region (Cowley et al, 2008).…”

Section: Role Of Thoracic Circuitry In Cervicolumbar Cpg Couplingmentioning

confidence: 99%

Cervicolumbar Coordination in Mammalian Quadrupedal Locomotion: Role of Spinal Thoracic Circuitry and Limb Sensory Inputs

Juvin¹,

Gal²,

Simmers³

et al. 2012

J. Neurosci.

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Effective quadrupedal locomotion requires a close coordination between the spatially distant central pattern generators (CPGs) controlling forelimb and hindlimb movements. Using isolated preparations of the neonatal rat spinal cord, we explore the role of intervening thoracic circuitry in cervicolumbar CPG coordination and the contribution to this remote coupling of limb somatosensory inputs. In preparations activated with bath-applied N-methyl-D,L-aspartate, serotonin, and dopamine, the coordination between locomotor-related bursts recorded in cervical and lumbar ventral roots was substantially weakened, although not abolished, when the thoracic segments were selectively withheld from neurochemical stimulation or were exposed to a low Ca 2ϩ solution to block synaptic transmission. Moreover, cervicolumbar CPG coordination was reduced after a thoracic midsagittal section, suggesting that cross-cord projections participate in the anteroposterior coupling. In quiescent preparations, either cyclic or tonic electrical stimulation of low-threshold afferent pathways in C8 or L2 dorsal roots (DRs) could elicit coordinated ventral root bursting at both cervical and lumbar levels via an activation of the underlying CPG networks. When lumbar rhythmogenesis was prevented by local synaptic transmission blockade, L2 DR stimulation could still drive left-right alternating cervical bursting in preparations otherwise exposed to normal bathing medium. In contrast, when the cervical generators were selectively blocked, C8 DR stimulation was unable to activate the lumbar CPGs. Thus, in the newborn rat, anteroposterior limb coordination relies on active burst generation within midcord thoracic circuitry that additionally conveys ascending and weaker descending coupling influences of distant limb proprioceptive inputs to the cervical and lumbar generators, respectively.

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“…In another set of experiments, the brain stem was stimulated using a suction electrode adhered to the ventrolateral surface (1.5-2.0 Hz, 45-80 pulses, 0.4-to 2.0-mA range). The stimulus electrode was fashioned out of a polyethylene tube (Intramedic PE50, Becton-Dickinson, 500 -600 m tip), and a ground pellet was placed adjacent to the brain stem (Zaporozhets et al 2004). For all stimulation protocols, Ն3 min was allowed between stimulation trains.…”

Section: Activation Of Cpgsmentioning

confidence: 99%

Interaction Between Developing Spinal Locomotor Networks in the Neonatal Mouse

Gordon¹,

Dunbar²,

Vanneste³

et al. 2008

Journal of Neurophysiology

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Gordon IT, Dunbar MJ, Vanneste KJ, Whelan PJ. Interaction between developing spinal locomotor networks in the neonatal mouse. J Neurophysiol 100: 117-128, 2008. First published April 24, 2008 doi:10.1152/jn.00829.2007. At birth, thoracosacral spinal cord networks in mouse can produce a coordinated locomotor-like pattern. In contrast, less is known about the cervicothoracic networks that generate forelimb locomotion. Here we show that cervical networks can produce coordinated rhythmic patterns in the brain stem-spinal cord preparation of the mouse. Segmentally the C 5 and C 8 neurograms were each found to be alternating left-right, and the ipsilateral C 5 and C 8 neurograms also alternated. Collectively these patterns were suggestive of locomotor-like activity. This pattern was not dependent on the presence of thoracosacral segments because they could be evoked following a complete transection of the spinal cord at T 5 . We next demonstrated that activation of thoracosacral networks either pharmacologically or by stimulation of sacrocaudal afferents could produce rhythmic activity within the C 5 and C 8 neurograms. On the other hand, pharmacological activation of cervical networks did not evoke alternating cervical rhythmic activity either in isolated cervicothoracic or -sacral preparations. Under these conditions, we found that activation of cervicothoracic networks could alter the timing of thoracosacral locomotor-like patterns. When thoracosacral networks were not activated pharmacologically but received rhythmic drive from cervicothoracic networks, a pattern of slow bursts with superimposed fast synchronous oscillations became the dominant lumbar neurogram pattern. Our data suggest that in neonatal mice the cervical CPG is capable of producing coordinated rhythmic patterns in the absence of input from lumbar segments, but caudorostral drive contributes to cervical patterns and rhythm stability.

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A reliable technique for the induction of locomotor-like activity in the in vitro neonatal rat spinal cord using brainstem electrical stimulation

Cited by 44 publications

References 31 publications

Flexibility of Motor Pattern Generation Across Stimulation Conditions by the Neonatal Rat Spinal Cord

Flexibility of Motor Pattern Generation Across Stimulation Conditions by the Neonatal Rat Spinal Cord

Cervicolumbar Coordination in Mammalian Quadrupedal Locomotion: Role of Spinal Thoracic Circuitry and Limb Sensory Inputs

Interaction Between Developing Spinal Locomotor Networks in the Neonatal Mouse

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