Lecture 18: Spinal Control of Movement Part 2

What are the characteristics of the gamma motor neurons?

• account for about 30% of motor axons in spinal nerve

• innervate intrafusal fibers of muscle spindles

• co-activated with alpha motor neurons to adjust tension of the muscle spindles

• are lined parallel with the extrafusal fibers

What does co-activation of alpha and gamma motor neurons do?

maintains the muscle spindle in its effective working range

What happens if there is no gamma motor neuron activation?

muscle spindle would go slack when extrafusal fibers contract, and muscle spindle would no longer encode changes in muscle length

What do gamma motor neurons set?

gain of spinal reflexes

What sets muscle tone?

regulation of gamma motor neurons by descending pathways from the pons

What does muscle tone regulation look like?

increase gamma activity → increased muscle stiffness

How is muscle tone assessed clinically?

passively extending and flexing the limbs

What causes hyper-reflexia?

loss of upper-motor neurons

What does the Golgi tendon organ do?

monitor muscle tension (force)

What class of axon is the golgi tendon organ?

class Ib: slightly smaller than Ia

What is the sensory receptor of the golgi tendon organ?

mechanoreceptors of skin

What is the diameter of the golgi tendon organ?

6-12 micrometers

What is the speed of the golgi tendon organ?

35-75 m/sec

What are golgi tendon organs in series with?

extrafusal fibers

What happens during an isometric muscle contraction (no length change)?

the muscle spindle activity (Ia) does not change, but the Golgi tendon organ (Ib) signals are increased in force

What happens during the reverse myotatic reflex?

• golgi tendon organ activity inhibits alpha motor neurons via inhibitory interneurons in spinal cord

• maintains muscle force at optimal level

What can happen to muscle with too much or too little force?

too much (Ib activity high): decreased alpha motor neuron activity

too little (Ib activity low): increased alpha motor neuron activity

What happens in patients with spasticity?

sustained force will eventually engage the Golgi tendon organs, and will cause muscle to relax

What causes spasticity?

upper motor neuron lesions

Where do alpha motor neurons get their inputs?

1. primary sensory axons

2. upper motor neurons from motor cortex

3. spinal interneurons (largest component)

What do primary sensory axons control?

muscle length, tension, pain, temperature, and touch

What do upper motor neurons from motor cortex control?

initiation and control of voluntary movement

What do spinal interneurons control?

spinal reflexes and motor programs

What happens in the agonist-antagonist stretch reflex circuit?

in response to muscle stretch, contraction of the stretched muscle (agonist) is accompanied by relaxation of the antagonistic muscle

What is inhibition of antagonist muscle mediated by?

inhibitory interneuron

What is the flexor reflex used for?

used to withdraw limb from aversive stimulus

What does the flexor reflex involve?

involved coordinated contraction of multiple muscles across multiple spinal segments

What would the flexor reflex look like if you stepped on a tack?

• tibialis anterior (calf): ankle flexion

• hamstring (posterior thigh): knee flexion

• hip flexion

Triple-flex reflex

What does the triple-flex reflex look like after upper motor neuron injury?

• The threshold drops. Mild, non-painful stimuli can set it off: stroking the sole (as in the Babinski test), light touch, bedsheets brushing the foot, or even passive movement.

• It is exaggerated. The withdrawal is stronger and more forceful than normal, and the whole leg jerks up into flexion.

• It spreads and lasts longer. The response can involve more muscles, last longer, or repeat as flexor spasms. In complete spinal cord injury, a strong stimulus can trigger a mass reflex. This is flexion of both legs, sometimes with bladder emptying and sweating.

• It accompanies the Babinski sign. The big toe extends upward (extensor plantar response), and the toes may fan. This toe extension is actually part of the same flexion-withdrawal synergy, which re-emerges when cortical control is lost.

What does the crossed-extensor reflex look like?

• activation of extensor muscles and inhibition of flexors on opposite side of body

• extends the right leg when lifting the left leg to avoid stepping on a tack

Where does the basic circuitry for walking reside?

in the spinal cord (similar to crossed-extensor reflex)

What does the rhythmic aspect of walking involve?

central pattern generators

What do central pattern generators do?

• individual spinal neurons can act as pacemakers

• intrinsic membrane properties of pacemaker neurons generate oscillatory patterns of activity and inactivity

What does the pacemaker activity via the NMDA mechanism look like?

In the presence of constant glutamate, an initial depolarization will cause:

1. membrane depolarization

2. removal of Mg²⁺ block from NMDA receptor

3. influx of Na⁺ and Ca²⁺ via NMDA channels

4. burst of spikes (accompanied by more Ca²⁺ entry)

5. opening of Ca²⁺-activated K⁺ channels

6. K⁺ efflux, membrane hyperpolarization

7. Mg²⁺ block of NMDA channels

8. no more Ca²⁺ influx

9. closing of Ca²⁺-activated K⁺ channels

10. membrane depolarization

What does removal of constant glucose do to the pacemaker activity of NMDA?

causes the cycle to stop

What does reciprocal inhibition of two pacemaker neurons provide?

a mechanism for generating alternating flexor-extensor activity

What happened when NMDA was applied to frog spinal cord?

NMDA switches on the spinal cord’s built-in swimming circuit, showing that rhythmic movement can be generated by the spinal cord alone, without the brain or sensory input.

What is Duchenne muscular dystrophy and what are the characteristics?

• a genetic abnormality in dystrophin

• X-linked, primarily occurs in male children starting before age 5

• generalized weakness and muscle wasting

• no neuronal involvement

What is dystrophin?

a protein that contributes to the muscular cytoskeleton; links actin filaments to plasma membrane

What is used to stand in Duchenne muscular dystrophoy? Why?

Gower’s maneuver because of the weakness in proximal muscles. Hands are stronger in this disease.

What is Myasthenia Gravis and what are the characteristics?

• autoimmune disorder in which the immune system mistakenly attacks nicotinic ACh receptors at the NMJ

• weakness, loss of control, particularly in eye and facial muscles

  • eyelid droop, double vision, chewing fatigue

How can Myasthenia Gravis be treated?

with AChE inhibitors, which increase the level and duration of ACh in the NMJ

What is ALS?

• degeneration of upper and lower motor neurons

• progressive loss of voluntary movement and muscle weakness

What causes the degeneration of upper and lower MNs in ALS?

• cause unknown (hypotheses: oxidative stress, mitochondria dysfunction, breakdown of cellular garbage collection, abnormal glial interactions)

• small fraction caused by genetic defect (familial ALS)

What causes the progressive loss of voluntary movement and muscle weakness in ALS?

• usually fatal within a few years due to respiratory failure

• fasciculations (spontaneous activations of motor units) are commonly seen

How does degeneration work in ALS?

both upper and lower motor neurons are affected, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken and waste away. Eventually, the ability of the brain to initiate and control voluntary movement is lost.