Muscle spindles and Golgi tendon organs

This chapter addresses Section L1(vi) from the 2023 CICM Primary Syllabus, which expects the exam candidates to "describe the monosynaptic stretch reflex, single twitch and tetanus". It represents a duplication of effort on the part of the author, whose younger self took it upon himself to address this subject in the "Reflex arcs" chapter probably because he felt that reflexes belonged more naturally in the neurology section. To make this look like new content, the focus of the discussion is biased in favour of the role of muscle, and specifically the specialised length and tension sensors in skeletal muscle.

  • Monosynaptic reflex arcs:
    • Reflex arcs consisiting of two neurons, i.e. with one synapse
    • Basic components consist of: 
      • Proprioception sensor organ (muscle spindle and Golgi tendon organ)
      • Afferent fibres, eg. sensory neuron axon
      • Processor organ, eg. α motor neuron (lower motor neuron)
      • Efferent fibres, eg. α motor axons
      • Effector organ, eg. muscle
    • Peripheral nerve (lower motor neuron) disease abolishes the reflex entirely
    • Spinal cord disease abolishes the reflexes at the level of the lesion and exaggerates them below the level of the lesion
  • Muscle spindles are fusiform encapsulated bundles of sensory fibres
    • All muscles except facial muscles contain these
    • Each spindle is bound to the outside of the perimysium of a fascicle
    • Responsible for the monosynaptyic stretch reflexes
  •  Intrafusal fibres are proprioceptive sensor organs inside muscle spindles
    • Specially modified muscle fibres, which remain contractile
    • Mainly sense muscle stretch and muscle length
    • Information about stretch is encoded into the rate of the afferent neuron firing
    • Innervated with fast afferent fibres (Group Ia and II)
    • Also receive efferent  γ-motor neuron innervation, so that they may contract in cohesion with the rest of the muscle and never becoem "slack", which would prevent them from accurately assessing the length information. 
  • Golgi tendon organs
    • Fusiform bundles of collagen fibres at the musculotendinous junction
    • Innervated with fast Group Ia fibres, and purely sensory (receive no efferents)
    • Mainly sense tendon stretch
    • Involved in di- and tri-synaptic reflex arcs which coordinate the synergistic inhibition of antagonist motor neurons, and mediate a reflexive relaxation of the same muscle when the tendon is stretched (inverse myotatic reflex).

As always with something like this, there is no single unifying resource that could be recommended, and the trainees must piece together their understanding from several separate papers or book chapters.

  • For monosynaptic reflexes, Clarac et al (2000) is an excellent detailed overview with delightful digressions into comparative biology. 
  • Nobody could do a better job of describing muscle spindles than Manuel Hulliger, who serenades them over 110 pages in his 1984 opus.
  • For Golgi tendon organs, Jami (1992) was the main resource used to complete this set of notes.

It is not essential, and perhaps even harmful, to direct the reader to these resources for exam revision, as CICM First Part exams have so far never included any muscle spindle content. The reader is warned that their time spent revising this material could be better spent on becoming more familiar with neuromuscular junction blockers.

Monosynaptic stretch reflex

The monosynaptic muscle stretch reflex represents the most basic level of proprioceptive position control for muscle, of which the simplest version consists of only three components: a contractile structure that senses stretch, and two neurons, one sensory and the other motor, connected by the single synapse that gives this thing the right to call itself "monosynaptic". That this simple mechanism might be widespread in the animal kingdom should surprise nobody, and it appears that basically anything with a nervous system tends to have these (seriously, ctenophores). The easiest way to represent it would be something like this:

simple monosynaptic reflex arc

In humans, most reflexes are polysynaptic (i.e involving an interneuron between the afferent and efferent cells), and monosynaptic reflexes are mostly limited to "deep tendon reflexes", i.e.  those you can bang with a reflex hammer during your hot case examination: 

  • Biceps (C5-6, musculocutaneous nerve)
  • Triceps (C7, radial nerve)
  • Quadriceps (L3-L4, femoral nerve)
  • Gastrocnemius (S1, tibial nerve)
  • Brachioradialis (C5-C6, radial nerve)

These are extensively modulated by descending fibres from the central motor cortex, where the modulation usually takes the form of inhibition, and is to some extent conscious (weird reflex facts include the way the descending inhibition is decreased, and in fact reversed, during sleep). However, all this sounds suspiciously like neurology, and there is plenty of reflex neurology elsewhere. To focus on muscle was the objective here. Apart from the effector role, muscle also contributes to monosynaptic reflex arcs by supplying the proprioceptive  stretch sensor organs, specifically muscle spindles and Golgi tendon organs.

Muscle spindles

"Spindle" is a term which was already archaic by the time it was first used by Kühne in 1863, as by that stage the textile industry had become sufficiently industrialised that nobody spun yarn manually anymore. The bottom line here is that this elongated organ is fusiform, which gives rise to the term intrafusal to describe its contents. the Journal of Physiology has some excellent high resolution images of the earliest depictions of muscle spindles by Angelo Ruffini (1898), and as is conventional,  Deranged Physiology will now challenge the reader's broadband connection by forcing them to download it inline with text:

Muscle spindle images by Ruffini (1898)

Of course the modern reader would probably be more interested in electron microscopy and immunofluorescence. Below, an excellent image from Gerwin et al (2020) shows off a nice single muscle spindle from a mouse soleus, fluorescing with the light of a probe against VGLUT1, a a glutamate transporter in the membrane of synaptic vesicles that acts as a neuron-specific marker.

A muscle spindle from a mouse soleus, by Gerwin et al, 2020

There was no scale associated with the image, but these things are said to be about  1-5mm long. They are small encapsulated bundles of specialised muscle fibres, swaddled together in some connective tissue and containing 8-20 intrafusal cells (Macefield & Knellwolf, 2018). Detailed analysis of muscle spindle physiology is probably not expected from the CICM exam candidate, but a few quotable spindle facts are probably worth knowing. Here's a list of possibly useful items extracted from the excellent paper by Kröger & Watkins (2021):

  • Practically all muscles contain several such spindles (except, for some reason, facial muscles), and they tend to occur with reasonably low density, such that Kröger & Watkins suggest there may only be about 50,000 of them in the entire human body.
  • They tend to be attached to the outside of the perimysial wall surrounding muscle fascicles, and therefore sense the "consensus" stretch of the entire muscle, rather than individual fibres.
  • When the surrounding muscle is stretched, the spindle is also stretched, and intrafusal fibres transduce this mechanical stretch stimulus into an afferent signal.
  • The information regarding the degree of muscle stretch is encoded into the rate of the afferent neuron firing, i.e. the more stretch there is, the higher the frequency of the firing (normally about 15 Hz at room temperature)
  • Rapid stretch is apparently more stimulating than slow stretch, where the stretched length remains the same.
  • Each spindle is innervated by Lloyd group Ia and group II afferent fibers, some of the fastest myelinated sensory fibres available to the human organism with a conduction velocity up to 120 m/sec. One possible clinically important aspect of this is the conduction delay, which leads to a lag between position sensation and the movement that corrects the position. The result is that proprioception is constantly chasing its own tail. We see this in the form of a fine (10Hz) physiological tremor, which is present in all mammals, and which frustrates fine motor tasks (such as microsurgery).
  • Each spindle also receives efferent γ-motor neuron innervation, which affects the minimalist contractile proteins of the intrafusal cells - this maintains cohesion of this sensory organ during muscle contraction, so that the contractile elements of the spinde co-activate together with the motor units of the muscle. If this did not happen, the spindles would become slack during muscle contraction, and lose their ability to sense stretch.

Which brings us to:

Intrafusal fibres

Yes, intrafusal cells remain contractile, in some awkward way. The "polar" regions on either end of the elongated cell contain just enough sarcomeres to remind you that these are actually heavily modified muscle fibres. They are much smaller and shorter than the rest of skeletal muscle fibres (rarely more than 25 μm in diameter); the length is only the same as the length of the spindle, which means most would be less than 5mm in length. They usually extend from one pole of the spindle to the other, spanning the entire length of the fusiform structure. The central region of each cell, described as "equatorial", is where all the sensory nerve endings are. Banks et al (1982) laboriously reconstructed these representations of that central region from hundreds of 1μm thick sections:

Intrafusal fibres from Banks et al, 1984

There are several distinct types of intrafusal fibres, named on the basis of what they do with their nuclei (i.e. there are "nuclear bag" and "nuclear chain" types), and beyond this there is a huge amount of subtle heterogeneity among them, with a different selection of fibre types deployed to different muscles (suggesting all kinds of functional specialisation). The mechanism of mechanotransduction here remains "largely unknown despite some tantalising clues", which is good for the CICM exam candidate, because it probably means there will be no exam questions about it; and so therefore one can make the broad generalisation that it would make no sense to go into any further detail here, as these matters are of very limited interest to the intensivist outside of their exams. 

Golgi tendon organs

It is generally said that muscle spindles monitor muscle length, and Golgi organs monitor muscle tension (Jami, 1992). Everybody who makes this statement seems to refer to a myology textbook from the 1970s as their main resource, and it is not clear what kind of experiments led to this conclusion, but the reader is reminded (to snatch back their wandering attention) that this is again a thing that a CICM trainee needs to know only enough about to pass a potential exam question, and no more. The following is therefore written in a pragmatic format, aiming to identify nuggets of potentially examinable gold among the mess of muscle histology.

  • Basically all the long-bodied muscles have tendon organs, as well as a few flat broad ones (eg. diaphragm)
  • They are not actually inside the tendons; they typically sit at the musculotendinous junction. Each muscle has several, and there seems to be one for every 2-3 motor units, such that there might be as few as 10 or as many as 80 per muscle (see this helpful table)
  • Each organ is usually a fusiform encapsulated structure made up of a long fascicle of collagen fibres attached to the tendon at one end, and to the terminal ends of a bouquet of several (up to 50) muscle fibres at the other. They are about the size of a muscle fibre themselves, perhaps up to 70-150 μm in diameter and up to 1000 μm in length. The capsule of each organ is a continuation of the perineurium of the fast (Type Ib) afferent fibre which innervated it (they do not have any contractile tissue in them, and do not receive efferents). Within the organ, mechanosensitive nerve endings ramify extensively between collagen fibres; when the tendon is stretched, these fibres are pushed together compressing and depolarising the sensory ending. 

In case a picture can be worth some number of words, here's a reconstruction of some sliced calf Golgi organs from Blumer et al (2003), which shows just enough fine structure to give a casual reader some idea of what this thing should look like. For a sense of scale, the length of the entire depicted organ is about 798 μm; they are usually much smaller than muscle spindles.

3d reconstruction of golgi tendon organ from Blumer et al (2003)

Of the two proprioceptive sensors in muscle, the muscle spindles are said to contribute the most to the proprioceptive feedback required for fine position adjustments and monosynaptic reflexes. The Golgi tendon organs mostly coordinate the synergistic inhibition of antagonist motor neurons, i.e they ensure that the triceps does not also contract while the biceps is contracting. This is in fact a di- or tri-synaptic reflex arc, as it involves one or two inhibitory interneurons. They also mediate a reflexive relaxation of the same muscle when the tendon is stretched, which is sometimes mentioned as the "inverse myotatic reflex". 

References

Clarac, François, Daniel Cattaert, and Didier Le Ray. "Central control components of a ‘simple’stretch reflex." Trends in neurosciences 23.5 (2000): 199-208.

Kass-Simon, G., and Paola Pierobon. "Cnidarian chemical neurotransmission, an updated overview." Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 146.1 (2007): 9-25.

Hulliger, Manuel. "The mammalian muscle spindle and its central control." Reviews of Physiology, Biochemistry and Pharmacology, Volume 101: Volume: 101 (1984): 1-110.

Kühne, W. "Die Muskelspindeln: Ein Beitrag zur Lehre von der Entwickelung der Muskeln und Nervenfasern." Archiv für pathologische Anatomie und Physiologie und für klinische Medicin 28.5-6 (1863): 528-538.

Ruffini, Angelo. "On the minute anatomy of the neuromuscular spindles of the cat, and on their physiological significance." The Journal of Physiology 23.3 (1898): 190.

Gerwin, Laura, et al. "Impaired muscle spindle function in murine models of muscular dystrophy." The Journal of physiology 598.8 (2020): 1591-1609.

Macefield, Vaughan G., and Thomas P. Knellwolf. "Functional properties of human muscle spindles." Journal of neurophysiology 120.2 (2018): 452-467.

Kröger, Stephan, and Bridgette Watkins. "Muscle spindle function in healthy and diseased muscle." Skeletal muscle 11.1 (2021): 1-13.

Cobo, Juan L., et al. "Searching for proprioceptors in human facial muscles." Neuroscience letters 640 (2017): 1-5.

Banks, Robert William, David Barker, and M. J. Stacey. "Form and distribution of sensory terminals in cat hindlimb muscle spindles." Philosophical Transactions of the Royal Society of London. B, Biological Sciences 299.1096 (1982): 329-364.

Bewick, Guy S., and Robert W. Banks. "Mechanotransduction in the muscle spindle." Pflügers Archiv-European Journal of Physiology 467 (2015): 175-190.

Allum, J. H., V. Dietz, and H. J. Freund. "Neuronal mechanisms underlying physiological tremor." Journal of Neurophysiology 41.3 (1978): 557-571.

Harwell, Richard C., and R. Lawrence Ferguson. "Physiologic tremor and microsurgery." Microsurgery 4.3 (1983): 187-192.

Jami, Léna. "Golgi tendon organs in mammalian skeletal muscle: functional properties and central actions." Physiological reviews 72.3 (1992): 623-666.

Blumer, Roland, et al. "Muscle spindles and Golgi tendon organs in bovine calf extraocular muscle studied by means of double-fluorescent labeling, electron microscopy, and three-dimensional reconstruction.Experimental eye research 77.4 (2003): 447-462.