Computational modeling of spinal circuits controlling limb coordination and gaits in quadrupeds

Danner, Simon M.; Shevtsova, Natalia A.; Frigon, Alain; Rybak, Ilya A.

doi:10.7554/elife.31050

Cited by 120 publications

(224 citation statements)

References 93 publications

(202 reference statements)

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“…One role of ipsilateral inhibition is to mediate flexor-extensor alternations via Ia reciprocal inhibition from V2b and V1 populations [18, 19]. Ipsilaterally descending propriospinal neurons may also stabilize left-right alternation, although specific ablation of inhibitory ipsilaterally descending neurons has not been tested [8, 59]. Our work establishes that selective suppression of V2b activity increases tail beat frequency (Fig.…”

Section: Discussionsupporting

confidence: 59%

“…Traditionally, patterned locomotion has been modeled as an alternation between excitation and inhibition, which dominate motor neurons during contraction and extension portions of the cycle, respectively [7, 8]. Recently, however, evidence from both fish and turtles has challenged the notion that inhibition is minimal during the contraction of the cycle, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control

Callahan¹,

Roberts²,

Sengupta³

et al. 2019

Preprint

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10The spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, 11 models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal 12 alternation between left and right sides or flexors and extensors. However, recent work has 13shown that inhibition also increases coincident with excitation during contraction. Here, using 14 larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-15 extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines 16 we define two stable subclasses with distinct neurotransmitter and morphological properties. 17These two V2b subclasses make direct synapses onto motor neurons with differential targeting to 18 slower and faster circuits. In vivo, optogenetic suppression of V2b activity leads to increases in 19 locomotor speed. We conclude that V2b neurons exert speed-specific influence over axial motor 20 circuits throughout the rostrocaudal axis. Together, these results indicate a new role for 21 ipsilateral inhibition in speed control. 22 46In-phase inhibition is thought to derive from two spinal interneuron classes, the V1 and V2b 47 populations. The V1 population includes Renshaw cells [15, 16], which provide recurrent 48 inhibition onto motor neurons with potentially significant shunting effects [17]. To date, most 49 analysis of drive from V2b neurons has focused on the shared contributions of V1s and V2bs to 50 reciprocal inhibition governing flexor/extensor alternation in limbed animals [18][19][20]. However, 51 this does not shed light on potential functions of ipsilateral inhibition in gain control for 52 regulation of motor neuron firing during contraction, as opposed to suppression of motor neuron 53 firing during extension. 54 55In-phase inhibition increases in amplitude for faster locomotor movements [10] suggesting a 56 potential role in speed control. Here we investigated whether V2b neurons could indeed provide 57 direct inhibition to motor neurons for speed control, taking advantage of the speed-dependent 58 organization of zebrafish motor circuits [21][22][23]. V2b neurons are good candidates for in-phase 59 gain control because they are exclusively inhibitory in mouse and zebrafish [24] with ipsilateral, 60 descending axons within the spinal cord [18, 25]. They arise from a final progenitor division that 61 produces pairs of V2a and V2b neurons [26]. Given the role of V2a neurons in triggering motor 62 output [27, 28], particularly through speed-specific circuits for titrating levels of motor excitation 63[4, 29-31], it seems plausible that their sister V2b neurons exert an opposing, inhibitory role in 64 speed control. However, the V2b class has not been well characterized at anatomical or 65 neurochemical levels outside of very early development. 66 67 5Here, we define two subclasses of V2b neurons in larval zebrafish based on differential 68 transmitter expression and anatomy, and further show that these neurons directly inhibit a...

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control

Callahan¹,

Roberts²,

Sengupta³

et al. 2019

Preprint

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“…In the present model, the organization of interactions between left and right RGs mediated by V0V and V0D populations of CINs followed that of our previous models (Ausborn et al, 2019;Danner et al, 2016Danner et al, , 2017Shevtsova et al, 2015;Shevtsova and Rybak, 2016). Specifically (see Figure 9), the populations of inhibitory V0D CINs provided direct mutual inhibition between the left and right flexor centers of the RGs, while the populations of excitatory V0V CINs mediated mutual inhibition between the same flexor centers through oligosynaptic pathways (each V0V population received excitation from the ipsilateral flexor center through a local population of V2a neurons and inhibited the flexor center of the contralateral RG through a population of local inhibitory neurons, Ini).…”

Section: Model Schematicmentioning

confidence: 67%

“…when some or all V0 CINs are genetically removed) and during gallop and bound. In our previous computational models (Danner et al, 2016(Danner et al, , 2017Rybak et al, 2013;Shevtsova et al, 2015;Shevtsova and Rybak, 2016), to perform this function the V3 CINs were assigned to explicitly mediate mutual excitation between the flexor centers of the left and right rhythm generators. However, our current experimental outcome contradicts this assumption, suggesting functional connection of V3 CINs to the contralateral extensor centers instead of the flexor centers.…”

Section: Coordination Of Left-right Activities By V3 Interneurons Durmentioning

confidence: 99%

“…Yet, the CIN networks promoting left-right synchronization at higher locomotor speeds, or during V0 ablation, are poorly understood. Previous modeling studies suggested that left-right synchronization could be performed by V3 CINs providing mutual excitation between the left and right rhythm-generating circuits (Danner et al, 2016(Danner et al, , 2017Rybak et al, 2013Rybak et al, , 2015Shevtsova et al, 2015;Shevtsova and Rybak, 2016). Although this suggestion allowed the previous models to reproduce the results of the above experimental studies, including the effects of V0 CIN ablation in vitro and in vivo, the role and connectivity of V3 neurons suggested by these models have not been tested experimentally and remained hypothetical.…”

Section: Introductionmentioning

confidence: 98%

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Spinal V3 interneurons and left-right coordination in mammalian locomotion

Danner

Zhang

Shevtsova

et al. 2019

Preprint

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Commissural interneurons (CINs) mediate interactions between rhythm-generating locomotor circuits located on each side of the spinal cord and are necessary for left-right limb coordination during locomotion. While glutamatergic V3 CINs have been implicated in left-right coordination, their functional connectivity remains elusive. Here, we addressed this issue by combining experimental and modeling approaches. We employed Sim1Cre/+; Ai32 mice, in which light-activated Channelrhodopsin-2 was selectively expressed in V3 interneurons. Fictive locomotor activity was evoked by NMDA and 5-HT in the isolated neonatal lumbar spinal cord. Flexor and extensor activities were recorded from left and right L2 and L5 ventral roots, respectively. Bilateral photoactivation of V3 interneurons increased the duration of extensor bursts resulting in a slowed down on-going rhythm. At high light intensities, extensor activity could become sustained. When light stimulation was shifted toward one side of the cord, the duration of extensor bursts still increased on both sides, but these changes were more pronounced on the contralateral side than on the ipsilateral side. Additional bursts appeared on the ipsilateral side not seen on the contralateral side. Further increase of the stimulation could suppress the contralateral oscillations by switching to a sustained extensor activity, while the ipsilateral rhythmic activity remained. To delineate the function of V3 interneurons and their connectivity, we developed a computational model of the spinal circuits consisting of two (left and right) rhythm generators (RGs) interacting via V0V, V0D and V3 CINs. Both types of V0 CINs provided mutual inhibition between the left and right flexor RG centers and promoted left-right alternation. V3 CINs mediated mutual excitation between the left and right extensor RG centers. These interactions allowed the model to reproduce our current experimental data, while being consistent with previous data concerning the role of V0V and V0D CINs in securing left-right alternation and the changes in leftright coordination following their selective removal. We suggest that V3 CINs provide mutual excitation between the spinal neurons involved in the control of left and right extensor activity, which may promote left-right synchronization during locomotion. V3 interneurons and left-right coordination2

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Control of Mammalian Locomotion by Somatosensory Feedback

Frigon

Akay

Prilutsky

2021

Comprehensive Physiology

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When animals walk overground, mechanical stimuli activate various receptors located in muscles, joints, and skin. Afferents from these mechanoreceptors project to neuronal networks controlling locomotion in the spinal cord and brain. The dynamic interactions between the control systems at different levels of the neuraxis ensure that locomotion adjusts to its environment and meets task demands. In this article, we describe and discuss the essential contribution of somatosensory feedback to locomotion. We start with a discussion of how biomechanical properties of the body affect somatosensory feedback. We follow with the different types of mechanoreceptors and somatosensory afferents and their activity during locomotion. We then describe central projections to locomotor networks and the modulation of somatosensory feedback during locomotion and its mechanisms. We then discuss experimental approaches and animal models used to investigate the control of locomotion by somatosensory feedback before providing an overview of the different functional roles of somatosensory feedback for locomotion. Lastly, we briefly describe the role of somatosensory feedback in the recovery of locomotion after neurological injury. We highlight the fact that somatosensory feedback is an essential component of a highly integrated system for locomotor control.

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Computational modeling of spinal circuits controlling limb coordination and gaits in quadrupeds

Cited by 120 publications

References 93 publications

Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control

Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control

Spinal V3 interneurons and left-right coordination in mammalian locomotion

Control of Mammalian Locomotion by Somatosensory Feedback

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