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Chalif Et Al 2022

Control of Animal Locomotion by Ventral Spinocerebellar Tract Neurons

Tags: #locomotion #CPG #central_pattern_generators #neuroscience #control #VSCT #fictive_locomotion

Related: [[An optimality principle for locomotor central pattern generators - Ryu Kuo 2021]] [[Human Central Pattern Generator - Does it Exist? Minassian 2017]]

Key Definitions

Spinocerebellar Tract: Nerve tract starting in the spinal cord leading to the cerebellum, has both a dorsal and ventral side. Ventral side conveys proprioceptive information from the body to the cerebellum

VSCT: Ventral spinocerebellar tract neurons, neurons located in the ventral side of the spinocerebellar tract that are being argued as candidates for CPGs in human locomotion

Afferent Neurons: Send sense data to the brain (ascending information)

Efferent Neurons: Send motor commands from brain to peripheral motor neurons (descending commands)

Optogenic Activation:

Chemogenetic Silencing:

Key Takeaways

  1. Human locomotion relies on spinal interneurons called CPGs that are responsible for alternating patterns between flexor-extensor muscles and between left-right side of the body. However it is unknown if one or multiple neuron types are responsible for locomotive control (is there one type of CPG neuron or many?).
    1. This study argues that one type of spinal neuron, the ventral spinocerebellar tract neurons (VSCTs) are necessary and sufficient to perform CPG functions
    2. Focuses on mice as experimental population
  2. VSCTs drive generation and maintenance of locomotor behavior in neonatal and adult mice
  3. VSCTs exhibit rhythmogenic properties and neuronal circuit connectivity consistent with their essential role in the locomotor CPG.
    1. VSCTs possess functional intrinsic properties consistent with a role in locomotor rhythmogenesis
    2. Motor neurons activate VSCTs via both chemical and electrical synapses
    3. VSCTs are able electrically communicate amongst themselves
    4. Experiments in cats show VSCTs have rhythmically modulated activity after deafferentation (removal of sense feedback to brain)
    5. Locomotor like activity can be induced through electric stimulation of mouse spinal cord
  4. Optogenetic activation and chemogenetic silencing reveals that VSCTs are necessary and sufficient for locomotion
    1. Optogenetic activation and chemogenetic silencing of VSCTs in postnatal mice indicate they are necessary and sufficient producing locomotor behaviour
      1. Photoactivation of VSCTs produced robust locomotor-like activity, showing activation of VSCTs is sufficient for locomotor behavior
      2. Photosilencing of VSCTs resulted in severe degradation of locomotor behaviour, and chemical silencing of VSCTs prevented both sensory and motor neuronaxon stimulation from inducing locomotor behavior, showing they are necessary as well
      3. There is also evidence that VSCTs are necessary and sufficient for maintaining, and not just inducing, locomotor behavior
      4. VSCTs send descending axon collaterals to caudal spinal seg- ments in addition to their main ascending axon to the cere- bellum.
  5. Chemogetic silencing of VSCTs in mobile adult mice perturbs their locomotor activities 1. Tested in swimming tasks as indicator of locomotor abilities - total time able to swim and stroke frequency were both affected
  6. Our findings identify an unexpected function for VSCTs as key controllers of mammalian locomotion and demonstrate that a single neuronal type is essential for such behavior, fundamentally changing the way we think complex behaviors are produced.
    1. Although the initiation of vertebrate locomotion takes place in the brain, and neurons in the brainstem can halt locomotion, the rhythm and pattern generation is solely produced by spinal neurons known as the locomotor CPG
    2. Electrical communication among spinal neurons is thought to be an important circuit mechanism in the locomotor CPG, and we argue that a key function of electrical coupling among VSCTs is to synchronize their activity.
    3. VSCTs are not purely a relay messenger of information as originally proposed
    4. Chx10+ spinal neurons receive significant activation by VSCTs during adult locomotion and without which the animal’s locomotor ability is significantly compromised.

Limitations

  1. Cannot fully exclude the potential involvement of DSCTs (dorsal spinocerebellar tract neurons) in locomotor behavior in adult mice as was demonstrated in neonatal mice.
  2. Locomotor like activity was found to be induced by stimulation of Motor Neuron axons, which is considered a puzzling observation, since MNs are thought to act solely as the mediators of central commands to skeletal muscles. 1. However, MNs have recently been proposed to provide feedback to the CPG during locomotor activity 2. There is the possibility that MNs may contact a yet-unknown interneuron that is key for the locomotor CPG.