Characterization of Sacral Interneurons That Mediate Activation of Locomotor Pattern Generators by Sacrocaudal Afferent Input

Etlin, Alex; Finkel, Eran; Mor, Yaniv; O’Donovan, Michael J.; Anglister, Lili; Lev-Tov, Aharon

doi:10.1523/jneurosci.4390-12.2013

Cited by 20 publications

(53 citation statements)

References 55 publications

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“…The most parsimonious hypothesis is that TRPV1 1 nSCAs (originating at S4) directly ascend multisegmentally beyond the L6 segment via Lissauer's tract and the dorsal column. We suggest that the direct multisegmental TRPV1 1 nSCA pathway-mediated activation of lumbar CPGs complements other indirect SCA pathways, which rely on relay interneurons in sacral segments (Etlin et al, , 2013. We first used an anatomical approach to investigate the extent of multisegmental projections of the S4 afferent collaterals along Lissauer's tract and the dorsal column.…”

Section: Resultsmentioning

confidence: 99%

“…Work by Lev‐Tov and colleagues examined projections from SCA afferents onto lumbar CPGs and found anatomical and electrophysiological evidence for relay interneurons being interposed at a sacral level (Strauss and Lev‐Tov, ). The sacral relay interneurons involved second‐order projections traveling via multiple white matter funiculi including the dorsolateral funiculus (DLF) (Etlin et al, ). The sacral second order projections could traverse across multiple segments to activate lumbar CPGs (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The term nSCA will be used here to denote TRPV1 1 collaterals as a subset of sacrocaudal afferents in the SCA pathway. The SCA pathways have been shown to be particularly effective in evoking locomotorlike activity in neonatal rats and mice (Lev-Tov et al, 2000;Whelan et al, 2000;Strauss and Lev-Tov, 2003;Blivis et al, 2007;Etlin et al, 2010Etlin et al, , 2013. The polymodal afferents in the SCA pathway have been shown to synapse onto sacral relay interneurons that in turn project several segments rostrally, via multiple white matter funiculi, to lumbar CPGs (Strauss and Lev-Tov, 2003;Etlin et al, 2010).…”

Section: Indexing Terms: Sacral Afferents; Trpv1; Cpgsmentioning

confidence: 99%

“…Unlike previous studies on second‐order relay projections (Etlin et al, ), here we focus on defining the direct projections of capsaicin‐sensitive TRPV1 + nSCA known to activate CPGs (Mandadi et al, ). Our hypothesis is that collaterals of TRPV1 + sacrocaudal afferents project rostrally along the tract of Lissauer and in the dorsal column (i.e., the fasciculus gracilis).…”

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confidence: 99%

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Identification of multisegmental nociceptive afferents that modulate locomotor circuits in the neonatal mouse spinal cord

Mandadi

Hong

Tran

et al. 2013

J of Comparative Neurology

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Compared to proprioceptive afferent collateral projections, less is known about the anatomical, neurochemical, and functional basis of nociceptive collateral projections modulating lumbar central pattern generators (CPG). Quick response times are critical to ensure rapid escape from aversive stimuli. Furthermore, sensitization of nociceptive afferent pathways can contribute to a pathological activation of motor circuits. We investigated the extent and role of collaterals of capsaicin-sensitive nociceptive sacrocaudal afferent (nSCA) nerves that directly ascend several spinal segments in Lissauer's tract and the dorsal column and regulate motor activity. Anterograde tracing demonstrated direct multisegmental projections of the sacral dorsal root 4 (S4) afferent collaterals in Lissauer's tract and in the dorsal column. Subsets of the traced S4 afferent collaterals expressed transient receptor potential vanilloid 1 (TRPV1), which transduces a nociceptive response to capsaicin. Electrophysiological data revealed that S4 dorsal root stimulation could evoke regular rhythmic bursting activity, and our data suggested that capsaicin-sensitive collaterals contribute to CPG activation across multiple segments. Capsaicin's effect on S4-evoked locomotor activity was potent until the lumbar 5 (L5) segments, and diminished in rostral segments. Using calcium imaging we found elevated calcium transients within Lissauer's tract and dorsal column at L5 segments when compared to the calcium transients only within the dorsal column at the lumbar 2 (L2) segments, which were desensitized by capsaicin. We conclude that lumbar locomotor networks in the neonatal mouse spinal cord are targets for modulation by direct multisegmental nSCA, subsets of which express TRPV1 in Lissauer's tract and the dorsal column. J. Comp. Neurol. 521:2870-2887, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Indexing Terms: Sacral Afferents; Trpv1; Cpgsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Identification of multisegmental nociceptive afferents that modulate locomotor circuits in the neonatal mouse spinal cord

Mandadi

Hong

Tran

et al. 2013

J of Comparative Neurology

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“…These facts suggest that Clarke's column does not simply relay peripheral sensory information to the cerebellum, but it also acts as a centre for specific actions 23–25. Information from the central pattern generator of the spinal cord may play a role in distinguishing sensory inputs that are a consequence of active locomotion from those attributable to perturbations in the external world 26. Therefore, an abnormality of Clarke's column may contribute to gait disturbance in two ways: (1) interference with actions that compensate for perturbations in rhythmic movement, and (2) delivery of erroneous proprioceptive information from the body periphery.…”

Section: Clarke's Column: a Centre For Locomotion And Stance?mentioning

confidence: 99%

Redefining cerebellar ataxia in degenerative ataxias: lessons from recent research on cerebellar systems

Tada

Nishizawa

Onodera

2015

J Neurol Neurosurg Psychiatry

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Recent advances in our understanding of neurophysiological functions in the cerebellar system have revealed that each region involved in degenerative ataxias contributes differently. To regulate voluntary movements, the cerebellum forms internal models within its neural circuits that mimic the behaviour of the sensorimotor system and objects in the external environment. The cerebellum forms two different internal models: forward and inverse. The forward model is formed by efference copy signals conveyed by the corticopontocerebellar system, and it derives the estimated consequences for action. The inverse model describes sequences of motor commands to accomplish an aim. During motor learning, we improve internal models by comparing the estimated consequence of an action from the forward model with the actual consequence of the action produced by the inverse model. The functions of the cerebellum encompass the formation, storage and selection of internal models. Considering the neurophysiological properties of the cerebellar system, we have classified degenerative ataxias into four types depending on which system is involved: Purkinje cells, the corticopontocerebellar system, the spinocerebellar system and the cerebellar deep nuclei. With regard to their respective contributions to the internal models, we speculate that loss of Purkinje cells leads to malformation of the internal models, whereas disturbance of the afferent system, corticopontocerebellar system or spinocerebellar system leads to mis-selection of the proper internal model. An understanding of the pathophysiological properties of ataxias in each degenerative ataxia enables the development of new methods to evaluate ataxias.

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Neuroanatomical basis for cholinergic modulation of locomotor networks by sacral relay neurons with ascending lumbar projections

Finkel

Etlin

Cherniak

et al. 2014

J of Comparative Neurology

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Synaptic excitation by sacrocaudal afferent (SCA) input of sacral relay neurons projecting rostrally through the ventral white matter funiculi (VF neurons) is a potent activator of the hindlimb central pattern generators (CPGs) in rodent spinal cords lacking descending supraspinal control. Using electrophysiological recordings from the sacral and lumbar spinal segments, we show that the motor output of the lumbar segments produced by SCA stimulation is enhanced by exposing the sacral segments of the neonatal rat spinal cord to the acetylcholinesterase inhibitor edrophonium (EDR). Histochemical and immunostaining of the sacral cord reveals expression of acetylcholinesterase activity, ability to synthesize acetylcholine, and/or innervation by cholinergic synaptic inputs in significant proportions of fluorescently back-labeled sacral VF neurons. Moreover, the majority of the VF neurons express M2 muscarinic receptors, raising the possibility that the elevated acetylcholine levels resulting from inhibition of acetylcholinesterase act on such receptors. Indeed, sacral application of atropine or the M2 -type receptor antagonist methoctramine was found to reverse the effects of EDR. We suggest that variations in the sacral level of acetylcholine modulate the SCA-induced locomotor rhythm via muscarinic receptor-dependent mechanisms and that the modified activity of sacral VF neurons in the presence of an acetylcholinesterase inhibitor can be partially ascribed to the cholinergic components associated with them. Thus, pharmacological manipulations of the sacral cholinergic system may be used to modulate the locomotor-related motor output in the absence of descending supraspinal control.

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Characterization of Sacral Interneurons That Mediate Activation of Locomotor Pattern Generators by Sacrocaudal Afferent Input

Cited by 20 publications

References 55 publications

Identification of multisegmental nociceptive afferents that modulate locomotor circuits in the neonatal mouse spinal cord

Identification of multisegmental nociceptive afferents that modulate locomotor circuits in the neonatal mouse spinal cord

Redefining cerebellar ataxia in degenerative ataxias: lessons from recent research on cerebellar systems

Neuroanatomical basis for cholinergic modulation of locomotor networks by sacral relay neurons with ascending lumbar projections

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