**2.1 Muscle spindles**

*Proprioception*

are mandatory.

**2. Proprioceptors**

cerebral process of proprioception.

transduction and the ion channel in this process.

ceptors are muscle spindles and Golgi's tendon organs.

those of conscious proprioception, are of capital interest to better understand this sense. The techniques of neuroimaging are providing new insights about the

Proprioceptors are a subset of mechanosensory neurons that provide afferent innervation to specialized sensory organs located inside the muscles and tendons, but probably also in joint capsules and ligaments, and the skin. According to Proske and Gandevia [4, 5] the sense of "*proprioception is achieved through a summation of peripheral sensory input describing the degree of, and changes in, muscle length and tension, joint angle, and stretch of skin*". In fact, the proper definition of proprioception coined by Sherrington in 1906 ("*In muscular receptivity we see the body itself acting as a stimulus to its own receptors—the proprioceptors*") suggest that the body contains different kinds of proprioceptors. Here we have focused on muscle spindles and Golgi's tendon organs. Especial interest was done on the mechanisms of mechano-

Proprioception originates by the activation of proprioceptors at the periphery.

Proprioception is impaired in some physiological and pathological situations. It will gain interest in the coming years due to the aging of population: the deficit of proprioception is associated with the increased frequency of falls in the elderly [6–8]. Furthermore, several diseases, especially some neurodegenerative disorders, course with proprioception deficits [9, 10] which treatment require a better knowl-

This chapter is aimed not to perform a Review on all the different aspects of proprioception but just to review some general and recent advances in proprioception. We intend to provide the readers of this book with an up-to-date appraisal of the structural and biological basis of proprioception. There are excellent reviews on the topic [4, 5, 11, 12] and we forward the interested to them. Robert W. Banks' extraordinary paper (2015) [13] masterfully sums up the history of knowledge of muscle spindles. Likewise, the recent reviews Kröger [14] Kröger and Watkins [1]

The peripheral receptors of proprioception are located in tissues around the joints, including skin, muscles, tendons, fascia, joint capsules, and ligaments [15] which contains different morphotypes of mechanoreceptors [16]. It is currently believed that proprioception is not generated by a single receptor, but by multiple of receptors. In any case proprioception has been related with sensory receptors localized in the muscles while kinesthesis has been more associated with joint and cutaneous receptors [17–19]. Nevertheless, the historically regarded as true proprio-

The *joints mechanoreceptors* are Ruffini-like and Pacinian corpuscles which signal

joint movement but not movement direction or joint position [15]. Regarding *cutaneous receptors* four kinds of mechanoreceptors are present in glabrous skin (Meissner's corpuscles, Pacinian corpuscles. Ruffini corpuscles and Merkel cellneurite complexes) [20–22]. A definitive role of cutaneous mechanoreceptors as proprioceptors has not been definitively established [23–25] although it is possible a convergence between cutaneous and muscle afferents at the spinal cord and

But independently of the modest contribution of cutaneous and articular mechanoreceptors to proprioception, the main stretch-sensitive receptors are muscle spindles found in most, but not all, skeletal muscles. For instance, they are absent form most cephalic muscles [26, 27]. Interestingly, muscle spindles are more

edge of the molecular aspects of proprioception and new active research.

**2**

thalamic levels.

Vertebrate muscle spindles are complex sensory organs that have both sensory and motor innervation. Each muscle spindle receives at least one sensory fiber that innervate specialized muscle fibers denominated intrafusal fibers. These intrafusal fibers also receive motor innervation by γ-motoneurons [30, 31]. Structurally, they are encapsulated mechanoreceptors, and functionally are slowly adapting-loth threshold mechanoreceptors [5].

Muscle spindles are highly variable in number from none in most cephalic muscles (see [27]) to numerous in lumbrical or deep neck muscles [32, 33]. These differences are attributed functional muscular demands of muscles but the number of muscle spindles per motor unit is rather equal [34]. Also, no topographical differences in muscle spindles between mono- and multiarticular muscles were noted [35].

Within the connective capsule that delimits each muscle spindles there are the intrafusal fibers and the periaxial space filled with a fluid. Three zones can be differentiated at the muscle spindle: the central or equatorial zone, the juxtaequatorial zone, and the terminal or polar zone; small segments of the intrafusal fibers can be found outside the poles of the muscle (**Figure 1**).

*The intrafusal muscle fibers.* Banks and co-workers [36] established that mammalian muscle spindles regularly contain three types of intrafusal muscle fibers. Based on their morphology and the arrangement of nuclei in the equatorial zone they fall into two main categories: nuclear bag fibers and nuclear chain fibers. Bag

#### **Figure 1.**

*Schematic representation of a muscle spindle and a Golgi's tendon organ. Muscle spindles are capsulated mechanoreceptors that consist of intrafusal muscle fibers (bag1, bag2 and chain), a periaxial space filled with a fluid, and a connective capsule. They are supplied by Ia (blue) and II (green) afferents. Golgi's tendon organs are capsulated mechanoreceptors that consist of collagen fibers and type Ia afferents (red).*

and chain fibers differs in structure, histochemical profile (myosin type, ATPase activity [37–39]) and functional properties. Bag fibers are greater in diameter and length than chain fibers, extend outside of the capsule, and they can be subdivided into bag1 and bag2 types (see for a review [40]). Human contains on average 8–20 intrafusal fibers and can lack bag1 or bag2 fibers [37].

As mentioned previously, muscle spindles are stretch detectors, i.e. "*they sense how much and how fast a muscle is lengthened or shortened*" [41]. Accordingly, when a muscle is stretched this change in length is transmitted to the intrafusal fibers which are in turn stretched. And to respond appropriately intrafusal fibers are double innervated by afferent sensory neurons and efferent motoneurons.

*Sensory innervation*. *"Just as the number of sensory endings varies from spindle to spindle, even within a single muscle, so also does the number of motor axons supplying those spindles"* [13].

There are two types of afferents that innervate intrafusal fibers: primary (type Ia) and secondary (type II) endings which differ in their axonal conduction velocity [13].

Each muscle spindle receives only one **Ia afferent** surrounding like a dock the equatorial zone of all the intrafusal fibers (spirals or annulospiral endings) (**Figure 1**). When spiral endings deform detect changes in length of the muscle. Primary afferents are sensitive to dynamic stretch, have irregular spontaneous or volitionally maintained discharge, and exhibit an off-response at the point of relaxation (i.e., muscle stretch) followed by a slow ramping isometric contraction; they are off during rapid voluntary contraction [13].

The number **type II afferent** endings in a muscle spindle varies from zero to five, and they supply one intrafusal fiber terminating mainly on nuclear chain fibers. The endings of the secondary afferents are spirals ending on the polar ends of the intrafusal fibers (**Figure 1**). Secondary afferents have a regular tonic discharge, and do not exhibit an off-response at the termination of a voluntary ramp-and-hold contraction [42, 43].

*Motor innervation.* In addition to sensory neurons, intrafusal muscle fibers are also innervated by efferent motoneurons (fusimotor innervation). Axons of motoneurons enter the muscle spindle together with the sensory fibers and innervate intrafusal fibers in the polar regions forming motor endplates.

Motor innervation originates from myelinated **γ-motoneurons** (diameter 4–8 μm), also known as fusimotor motoneurons. They have been differentiated into static and dynamic. Dynamic axons have a weak effect on primary afferent firing while the static ones have a great influence on both primary and secondary afferents (see [43]).

Occasionally additional afferent innervation of muscle spindles originates from axons that also supply extrafusal muscle, known as **β-motoneurons** or skeletofusimotor fibers. These fibers supply both intrafusal and extrafusal fibers via motor endplates at the polar ends. The endplates of γ-motoneurons differ structurally from those formed by α-motoneurons on extrafusal fibers, but both are cholinergic synapses with many features in common, including junctional folds and a basal lamina filling the synaptic cleft. [42–46].

Stimulation of γ-motoneurons result in excitation of both Ia and II muscle spindle afferents. On the other hand, stimulation of **α-motoneurons** supplying extrafusal muscle fibers, results in coactivation of γ-motoneurons which in turn causes the contraction of the polar ends of the intrafusal fibers, restoring tension and sensitivity of the muscle spindle to stretch.

Thus, the γ-motoneuron function control the sensitivity of muscle spindle afferents as length detectors. Therefore, the muscle spindle's function as a length

**5**

*Structural and Biological Basis for Proprioception DOI: http://dx.doi.org/10.5772/intechopen.96787*

**2.2 Golgi's tendon organ (tendon spindle)**

muscle tension via its Ib afferent (**Figure 1**).

series between muscle and tendon.

replenishment mechanism.

the muscle spindle [44].

sensor arises essentially from its anatomical relationship with its parent muscle. Any length change in the parent muscle result in stretch of intrafusal fibers that is then detected by sensory receptors located on the equatorial and polar regions of

The Golgi-tendon organ or tendon-spindle, localized at the origins and insertion of tendon, or rarely within the tendon. It is a mechanoreceptor that informs on

Structurally it consists of a capsule and within it there are loosely packed collagen fibers and muscle fibers (3–50). Among these elements there is a unique Ia afferent which branches to innervate the distal and the proximal parts of the organ [28, 47]. With respect to the skeletal muscle fibers the Golgi-tendon organ is in

The Golgi-tendon model react to "static and dynamic responses to activation of single motor units whose muscle fibers insert into the Golgi tendon organ, self and cross adaptation, non-linear summation when multiple motor units are active in the muscle, and the proportional relationship between the cross-adaptation and

The sensory terminals of muscle spindles appear to adhere to the surface of the intrafusal muscle fibers, and although they possess a basal lamina in close contact

Bewick and co-workers [44] have demonstrate the occurrence of a complete gutamatergic neurotransmission system in the afferents of muscle spindles associated to the synaptic-like vesicles typical of those terminals. Exogenous glutamate enhances spindle excitability, an effect that can be pharmacologically blocked with specific molecules. On the other hand, synaptic-like vesicles contain glutamate, which is released during membrane cycling and, subsequently, a requirement for a

This observation, however, does not exclude the possibility that other neuroac-

In addition to the possible classical neurotransmission, the primary mechanism of mechanical transduction in muscle spindle sensory endings is the activation of stretch-sensitive ion channels. In mechanotransduction, i.e. the conversion of mechanical stimuli into biological or electrical signal, is triggered by members of

acid-sensing ion channels -ASIC-), transient receptor potential channels (TRP), two-pore domain potassium (K2p), and PIEZO [49, 50]. Some of them have been detected directly in proprioceptors as well as in primary sensory neurons innervating them. However, and similarly as in cutaneous mechanoreceptors, the stretch-sensitive channels responsible for transducing mechanical stimuli in spindle


C; including

summation recorded for various pairs of motor units" [47, 48].

with the plasmalemma it is absent at the sensory terminals.

tive substances also occur in these sensory terminals.

the superfamilies of degenerin-epithelial Na+

afferents awaits definitive identification (see [51]).

**3.2 Ion channels and mechanorasduction in muscle spindles**

**3.1 Afferent glutamate-ergic neurotransmision in muscle spindles?**

**3. Mechanotransduction in muscle spindles**

*Proprioception*

motoneurons.

velocity [13].

*those spindles"* [13].

and chain fibers differs in structure, histochemical profile (myosin type, ATPase activity [37–39]) and functional properties. Bag fibers are greater in diameter and length than chain fibers, extend outside of the capsule, and they can be subdivided into bag1 and bag2 types (see for a review [40]). Human contains on average 8–20

As mentioned previously, muscle spindles are stretch detectors, i.e. "*they sense how much and how fast a muscle is lengthened or shortened*" [41]. Accordingly, when a muscle is stretched this change in length is transmitted to the intrafusal fibers which are in turn stretched. And to respond appropriately intrafusal fibers are double innervated by afferent sensory neurons and efferent

*Sensory innervation*. *"Just as the number of sensory endings varies from spindle to spindle, even within a single muscle, so also does the number of motor axons supplying* 

There are two types of afferents that innervate intrafusal fibers: primary (type Ia) and secondary (type II) endings which differ in their axonal conduction

Each muscle spindle receives only one **Ia afferent** surrounding like a dock the equatorial zone of all the intrafusal fibers (spirals or annulospiral endings) (**Figure 1**). When spiral endings deform detect changes in length of the muscle. Primary afferents are sensitive to dynamic stretch, have irregular spontaneous or volitionally maintained discharge, and exhibit an off-response at the point of relaxation (i.e., muscle stretch) followed by a slow ramping isometric contraction;

The number **type II afferent** endings in a muscle spindle varies from zero to five, and they supply one intrafusal fiber terminating mainly on nuclear chain fibers. The endings of the secondary afferents are spirals ending on the polar ends of the intrafusal fibers (**Figure 1**). Secondary afferents have a regular tonic discharge, and do not exhibit an off-response at the termination of a voluntary

*Motor innervation.* In addition to sensory neurons, intrafusal muscle fibers are also innervated by efferent motoneurons (fusimotor innervation). Axons of motoneurons enter the muscle spindle together with the sensory fibers and innervate

Occasionally additional afferent innervation of muscle spindles originates from

axons that also supply extrafusal muscle, known as **β-motoneurons** or skeletofusimotor fibers. These fibers supply both intrafusal and extrafusal fibers via motor endplates at the polar ends. The endplates of γ-motoneurons differ structurally from those formed by α-motoneurons on extrafusal fibers, but both are cholinergic synapses with many features in common, including junctional folds and a basal

Stimulation of γ-motoneurons result in excitation of both Ia and II muscle spindle afferents. On the other hand, stimulation of **α-motoneurons** supplying extrafusal muscle fibers, results in coactivation of γ-motoneurons which in turn causes the contraction of the polar ends of the intrafusal fibers, restoring tension

Thus, the γ-motoneuron function control the sensitivity of muscle spindle afferents as length detectors. Therefore, the muscle spindle's function as a length

Motor innervation originates from myelinated **γ-motoneurons** (diameter 4–8 μm), also known as fusimotor motoneurons. They have been differentiated into static and dynamic. Dynamic axons have a weak effect on primary afferent firing while the static ones have a great influence on both primary and secondary

intrafusal fibers and can lack bag1 or bag2 fibers [37].

they are off during rapid voluntary contraction [13].

intrafusal fibers in the polar regions forming motor endplates.

ramp-and-hold contraction [42, 43].

lamina filling the synaptic cleft. [42–46].

and sensitivity of the muscle spindle to stretch.

afferents (see [43]).

**4**

sensor arises essentially from its anatomical relationship with its parent muscle. Any length change in the parent muscle result in stretch of intrafusal fibers that is then detected by sensory receptors located on the equatorial and polar regions of the muscle spindle [44].
