Progress in Brain Research, Vol.

151
ISSN 0079-6123
Copyright r 2006 Elsevier B.V. All rights reserved

CHAPTER 3

Sensory control of extraocular muscles

J.A. Büttner-Ennever1,, K.Z. Konakci2 and R. Blumer2

1
Institute of Anatomy, Ludwig-Maximilian University of Munich, Pettenkoferstrasse 11, D-80336 Munich, Germany
2
Center of Anatomy and Cell Biology, Medical University of Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria

Abstract: The role of sensory receptors in eye muscles is not well understood, but there is physiological and
clinical evidence for the presence of proprioceptive signals in many areas of the central nervous system. It is
unclear which structures generate these sensory signals, and which central neural pathways are involved.
Three different types of receptors are associated with eye muscles: (1) muscle spindles, (2) palisade endings,
and (3) Golgi tendon organs, but their occurrence varies wildly between species. A review of their or-
ganization shows that each receptor is mainly confined to a morphologically separate layer of the eye
muscle. The palisade endings — which are unique to eye muscles, are associated with the global layer; and
they have been found in all mammals studied so far. Their function is unknown. The muscle spindles, if
they are present in a species, lie in the orbital layer, or at its junction to the global layer. Golgi tendon
organs appear to be unique to artiodactyls (i.e., sheep and goats, etc.); they lie in an outer distal marginal
layer of the eye muscle, called the ‘‘peripheral patch layer’’ in sheep. The specific association between
palisade endings and the multiply innervated type of muscle fibers of the global layer has led to the
hypothesis that together they may act as a sensory receptor, and provide a source of central proprioceptive
signals. But other interpretations of the morphological evidence do not support this role.

Introduction tension during converged gaze (Miller, 2003),

The sensory control of eye muscles has been stead-
fastly ignored in terms of modeling or integration
into the understanding of eye movements, in spite
of the fact that there is a large weight of information
showing that eye muscle possess a proprioceptive
system (reviews: Steinbach, 1987; Ruskell, 1999;
Donaldson, 2000; Weir et al., 2000; Büttner-Ennever
et al., 2003). For example, spatial localization
in humans can be altered by either pulling eye
muscles (Lewis and Zee, 1993), by strabismus
surgery (Steinbach and Smith, 1981; Dengis et al.,
1998), or section of the trigeminal nerve in the
treatment of trigeminal neuralgia (Ventre-Dominey
et al., 1996). Anomalous values in eye muscle
Corresponding author. Tel.: +49 89 5160 4851;
Fax: +49 89 5160 4857;
E-mail: jean.buettner-ennever@med.uni-muenchen.de
could be explained on the basis of the control of
tension in extraocular muscles by proprioceptors
(Miller, 2003). Stretching the eye muscles, or elec-
trically stimulating them in animals evokes
responses in areas such as the mesencephalic trige-
minal nucleus (Alvarado-Mallart et al., 1975),
superior colliculus (Abrahams, 1979; Donaldson
and Long, 1980), visual cortex (Fiorentini and
Maffei, 1977), the cerebellum and nucleus prep-
ositus (Ashton et al., 1988). Anatomical tracing
studies have demonstrated projections from the
eye muscle through the trigeminal ganglion into
the spinal trigeminal nucleus (Batini et al., 1975;
Porter, 1986; Ogasawara et al., 1987; Buisseret-
Delmas and Buisseret, 1990; Buisseret, 1995), in
ungulates in the mesencephalic trigeminal nucleus
(Bortolami et al., 1987), in the superior colliculus
(Ndiaye et al., 2000), the vestibular nuclei (Buisseret
-Delmas and Buisseret, 1990), prepositus hypoglossi

DOI: 10.1016/S0079-6123(05)51003-3 81
82
nucleus and the cerebellum (Batini et al., 1974;
Kimura et al., 1991). Cutting the ophthalmic nerve
(deafferentation) causes fixation instability (Fiorentini
and Maffei, 1977) and reduction in stereoacuity in
cat (Maffei and Fiorentini, 1976), and deviation of
eye position in lambs (Pettorossi et al., 1995).
Lastly, and of most significance, is that eye
muscles contain proprioceptive end-organs —
muscle spindles and Golgi tendon organs. They
also have palisade endings, but their function is
still controversial (Ruskell, 1999, Konakci et al.,
2005). There are several excellent reviews on this
topic (Ruskell, 1999; Donaldson, 2000; Weir et al.,
2000; Lewis et al., 2001).
Alongside the evidence for the existence of func-
tional proprioception in eye muscles a large body
of counter evidence exists. No stretch reflex could
be recorded in abducens motor units when the
ipsi-eye was pulled (Keller and Robinson, 1971).
Cutting the ophthalmic nerves in monkey (assumed
to achieve deafferentation) gave very little effect on
saccades (Guthrie et al., 1983), smooth pursuit,
vestibular responses, conjugacy, adaptation, ocular
alignment etc. (Lewis et al., 2001). Finally, the
presence of eye muscle proprioceptors varies wildly
between species, and in some cases proprioceptors
appear not to be present at all (Ruskell, 1999;
Donaldson, 2000). These features do not correlate
with any known eye movement properties, and it
has proved hard to find a clear concept. In this
review we will present the current neuroanatomical
and morphological evidence for proprioception in
eye muscles, suggest various hyptheses, and show
that there is room for differences in interpretation
concerning the basis for eye muscle proprioception,
even between the authors of this chapter.
Layered structure of eye muscles
Eye muscles have an unusual feature, they have
two to three separate morphological subdivisions,
which have independent developmental features
(Porter et al., 1995). There is an inner ‘‘global’’
layer, an outer ‘‘orbital’’ layer, and in sheep
(artiodactyls) a distinct third muscle layer, first
described by Harker (1972). It lies mainly distally
in a C-shape around the outside of the orbital
layer, and he called it the ‘‘peripheral patch layer.’’
A similar layer was described in humans by Wasicky
et al. (2000), and called the marginal layer. Its pres-
ence in other species is unclear. The two main eye
muscle layers found in all mammals have several
important differences: the global layer inserts
through the tendon on the sclera of the globe:
whereas the orbital layer inserts onto Tenon’s
capsule, which is a ring of fibroelastic connective
tissue that lies around the equator of the eyeball
and forms sleeves around the individual eye
muscles. Recently the role of Tenon’s capsule in
directing the pulling direction of the eye muscles
has been widely discussed, and it has been referred
to as ‘‘the pulleys’’ (see Chapters 1 and 2) (Porter
et al., 1996; Demer et al., 2000).
The types of muscle fibers in each layer have
been reviewed in Chapter 2; however, it is impor-
tant to point out that the multiply innervated
muscles fibers (MIFs), or nontwitch muscle fibers,
occur in all three layers. The MIF fiber type
belongs to a whole spectrum of fibers found in the
skeletal muscles of lower vertebrates and birds
(Morgan and Proske, 1984). Their action poten-
tials are non-propagated, they have a slow tonic
firing rate, and are highly unfatiguable. In mammals,
MIFs are found almost exclusively in eye muscles,
and then primarily in the global layer where they
run the whole length of the muscle (Mayr et al.,
1975). The muscle fibers of the orbital layer have a
MIF structure at the poles but it changes along its
length in the central region to a twitch type, singly
innervated muscle fiber (Pachter, 1984). This
distinction has some importance when consider-
ing the association of sensory structures (palisade
endings) to the global MIFs, see below.
Proprioceptors
Muscle spindles
Muscle spindles in eye muscles
All skeletal muscles possess muscle spindles, so it is
curious that in extraocular muscles some animals
have them, and others lack them: no muscle spin-
dles have been found in the eye muscles of sub-
mammalian species (Maier et al., 1974). Many

mammalian species do not have muscle spindles in
their eye muscles: most monkey species including
Macacca fascicularis, dogs, cats, rats, guinea pigs,
and rabbits do not have muscle spindles; whereas
they have been found in humans (Cilimbaris, 1910;
Lukas et al., 1994), and a few in some species of
monkey such as rhesus (Greene and Jampel, 1966;
Maier et al., 1974), as well as mice (Mahran and
Sakla, 1965) and all ungulates (artiodactyls)
(Cilimbaris, 1910; Blumer et al., 2003). An analysis
of the literature shows that the density of muscle
spindles in human eye muscles is extremely high
and is comparable to the density of muscle
spindles in hand lumbrical and short neck mus-
cles (see Table 1) (Lukas et al., 1994). The
distal–proximal distribution of spindles in the
individual muscles in human is shown in Fig. 1.
However, when the organization is analyzed in
terms of muscle layers, it becomes obvious from
cross sections of the eye muscle that muscle spindles
are associated with the orbital layer, or the
transition zone of the orbital layer with the global
layer: but they are not associated with the
global layer (sheep: Harker, 1972; monkey: Greene
and Jampel, 1966; human: Cilimbaris, 1910; Ruskell,
1989, 1999; Lukas et al., 1994; Blumer et al., 1999).
This is shown in Cilimbaris’ original drawing of
sheep lateral rectus in Fig. 2. It has long been
known that MIFs are also closely associated with
muscle spindles: branches from extraocular MIFs
enter the sheep muscle spindles and build nuclear
bag fibers (Harker, 1972; Baker, 1974; Morgan
and Proske, 1984). It is significant that the muscle
spindles of sheep (artiodactyls) eye muscles are an
exception in that they are well developed, and
hence very similar to those of skeletal muscle
(Harker, 1972).
Muscle spindles in skeletal muscle
In skeletal muscles it is well established that
sensory information used for motor control is
generated by muscle spindles, and Golgi tendon
organs. The skeletal muscle spindles contain three
types of intrafusal muscle fiber, termed nuclear
chain, nuclear bag1, and nuclear bag2 fibers (Walro
and Kucera, 1999). Nuclear bag1 intrafusal fibers
of muscle spindles also have the same heavy-chain
myosin as the MIFs (Pedrosa-Domellof et al.,
83
1991). Each skeletal spindle receives innervation
from a sensory afferent in its equatorial region,
and the polar regions of the intrafusal muscle fibers
receive gamma-motor (g-) innervation to maintain
the sensitivity of the muscle spindle during muscle
shortening. Both intrafusal and extrafusal muscle
fibers develop by a similar process in the late
gestational period, whereby myoblasts fuse into
myotubes, however the intrafusal fibers remain
much shorter and thinner (Kucera et al., 1993).
The occurrence of muscle spindles in skeletal muscles
has been recently shown to be a highly dynamic
process. For example their incidence is critically
dependent on the timing of the sensory innervation
of the developing spindles. If the sensory afferent
is cut, then, depending on the developmental
period, muscle spindles may fail to develop, or
undergo degeneration and hypertrophy into a
structure indistinguishable from an extrafusal fiber
(Kucera et al., 1993). Furthermore, the application
of nerve growth factor during the redevelopment
of the cut sensory nerve, leads to the formation of
countless supernumery muscle spindles (Sekiya
et al., 1986). Similar changes in the occurrence of
muscle spindles in skeletal muscles have been
shown to be dependent not only on neurotrophins,
but also specific genetic transcription factors
(Sekiya et al., 1986; Walro and Kucera, 1999;
Fan et al., 2000; Kucera et al., 2002).
Comparison of extraocular and skeletal muscle
spindles
The occurrence of muscles spindles in eye muscles,
as explained above, is extremely variable between
species; this is not the case with skeletal muscles. A
second difference is that in general the extraocular
muscle spindles appear poorly preserved in com-
parison to those in skeletal muscle, even to the
point that some authors have raise the question of
whether or not they are functional (Ruskell, 1989,
1999; Blumer et al., 1999; Bruenech and Ruskell,
2000, 2001). A cross section of the human extra-
ocular muscle spindle is shown in Fig. 3. Most
muscle spindles lack an expansion of the equato-
rial zone. All muscle spindles contain fibers of the
nuclear chain type, but no nuclear bag fibers, are
present. Furthermore, extraocular muscle spindles
also have many anomalous fibers which pass
84

Table 1. Number of muscle spindles in human extraocular muscles (Lukas et al. 1994)

Individuals Mean7standard deviationa

1 2 3
72a 83a 67a
Female Female Male

Right Left Right Left Right Left

Medial rectus 5b 15 19 20 17 23 18.873.0, n ¼ 5

Lateral rectus 21 22 18 17 19 19 19.371.9, n ¼ 6
Superior rectus 17 16 13 14 20 15 15.872.5, n ¼ 6
Inferior rectus 30 36 33 31 42 32 34.074.4, n ¼ 6
Superior oblique 24 22 22 21 41 34 27.378.2, n ¼ 6
Inferior oblique 3 7 3 6 4 3 4.371.8, n ¼ 6
Orbitc 100d 118 108 109 143 126 120.8714.4, n ¼ 5
a
Mean7standard deviation of counts in 6 (5b) specimens of this muscle. b Incomplete count due to technical reasons in parts of this
specimen. c Total number of spindles in all extraocular muscles of this orbit. d Incomplete total.

Fig. 1. The location of muscle spindles in human extraocular muscles (Lukas et al., 1994).

through the muscle spindle capsule without any
intrafusal modification. An exception to this is
seen in ungulates where the extraocular spindles
have none of these differences, and they appear
very similar to the skeletal spindles (Harker, 1972;
modified from Blumer et al., 2003).
In the light of the multiple factors known to
affect the development of muscle spindles in skel-
etal muscles, it is not surprising that there is a wide
variation in the presence or absence of muscle
spindles found in extraocular muscles. The eye
muscle has different layers (global and orbital)
maturing at different times, and how this is coor-
dinated with the development of sensory and
motor innervation is completely unknown (Porter
et al., 1995; Cheng et al., 2003, 2004). However,
one can be certain that it will vary between species.
Palisade endings
If the orbital layer uses muscle spindles to generate
its sensory signals what does the global layer use?
The global layer possesses an unusual feature
 85

Fig. 2. Drawings modified from the sketches of Cilimbaris (1910) from lateral rectus of the sheep. Note that muscle spindles (white
circles with central black dots) lie in, or close to, the orbital layer.

Fig. 3. (A) Semithin cross section through a human extraocular muscle spindle. The muscle spindle contains six nuclear chain fibers
(NCF) and one anomalous fiber (AF). An associated muscle fiber (ASF) is running between the capsule (C); nerve (N); scale bar, 50 mm
(Blumer et al., 1999). (B) Human extraocular muscle spindle. Ultrathin cross section through a nuclear chain fiber with a sensory nerve
terminal (ST) containing mitochondria. Basal lamina (BL); scale bar, 1 mm. Inset: line drawing of the region of interest. Nuclear chain
fiber (NCF) with a central nucleus (N) (modified from Blumer et al., 1999).

unique to eye muscles, it has palisade endings at the
myotendinous junctions (Dogiel, 1906; Cilimbaris,
1910; Ruskell, 1999). Palisade endings have been
found in almost all species that have been inves-
tigated, including the rat (Eberhorn et al., 2005).
Several authors have suggested that palisade end-
ings could be the source of sensory afferent signals
(Ruskell, 1999; Donaldson, 2000; Weir et al., 2000;
Büttner-Ennever et al., 2002); but there still con-
flicting reports on the functional nature of palisade
86
endings, whether they are sensory or motor struc-
tures, or both (Lukas et al., 2000; Konakci et al.,
2005).
Palisade endings form a cuff of nerve branches
around the muscle fiber tip, like a palisade fence;
but they contact only one type of muscle fiber, the
MIFs of the global layer (Mayr, 1977; Alvarado-
Mallart and Pincon Raymond, 1979; Richmond
et al., 1984; Ruskell, 1999). The term ‘‘innervated
myotendinous cylinders’’ is used to describe the
palisade endings along with their fibrous capsule.
The palisade terminals arise from nerve fibers that
enter the tendon from the central nerve entry zone,
and then turn back 1801, to contact the tip of the
muscle fibers (Fig. 4). Detailed ultrastructural
studies of palisade endings have been made in
monkey (Ruskell, 1978), cat (Alvarado-Mallart
and Pincon Raymond, 1979), sheep (Blumer et al.,
1998), rabbit (Blumer et al., 2001), and human
(Sodi et al., 1988; Lukas et al., 2000). In the vast
majority of cases the palisade terminals, covered
by an intact basal membrane, made intimate
Fig. 4. Palisade endings in an extraocular rectus muscle of a
cat, viewed by a confocal laser scanning microscope. Nerve fi-
bres (red) come in from the right pass up to the tendon, then
turn back to form palisade endings around the muscle fiber tip.
Nerve fibers are labeled with antineurofilament, nerve terminals
(green) with antisynaptophysin. Muscle fibers are stained with
phalloidin. Scale bar, 50 mm (Konakci et al., 2005).
contact with the collagen fibrils, which is analogous
to the nerve terminals in Golgi tendon organs
(Lukas et al., 2000; Konakci et al., 2005). Such
nerve terminals are arguably sensory in nature.
Similar results were found in monkey, cat, and
sheep.
Interestingly, a few palisade terminals made
neuromuscular, as apposed to the more usual
neurotendinous, contacts, and at the point of
contact with the muscle membrane they lacked a
basal lamina; these structures resemble in some
ways sensory nerve terminals on intrafusal fibers in
muscle spindles (Fig. 5A and B) (Kubota, 1988;
Ruskell, 1989; Blumer et al., 1999, 2003; Konakci
et al., 2005). A few neuromuscular junctions were
also reported by Richmond et al. (1984) in palisade
endings of humans.
In palisade endings of humans, Lukas et al.
(2000) have found sensory-like neurotendinous
contacts and motor neuromuscular contacts: and
the authors daringly propose that palisade endings
might combine sensory and motor function. The
terminals of rabbit palisade endings were unique,
in that they all possessed a basal lamina, they were
all neuromuscular and bound a-bungarotoxin,
thereby resembling motor terminals (Blumer
et al., 2001).
Recently, Konakci et al. (2005) have demon-
strated in cats that palisade endings are cholinergic
structures. Palisade endings are supplied by nerve
fibers which stain positively for choline acetyl-
transferase and the palisade-ending terminals
(neurotendinous and neuromuscular contacts) are
choline acetyltransferase immunoreactive too. Only
the sparse neuromuscular contacts are positive for
a-bungarotoxin as well — a feature of motor
terminals. The presence of sparse acetylcholine
receptors at the myotendinous region, which bind
a-bungarotoxin, has been found on singly and
multiply innervated muscle fibers of frog muscle
(Miledi et al., 1984).
The uncertainty concerning the sensory or
motor nature of palisade endings is compounded
by the conflicting evidence on the location of their
cell somata. If the palisade endings are sensory
their ganglion cell body should be in the trigeminal
ganglion or in the mesencephalic trigeminal
nucleus; whereas if the endings are of a motor
 87

Fig. 5. (A) A neurotendinous terminal of a palisade ending in cat extraocular muscle. A nerve terminal (NT) is making contact to the
surrounding collagen fibrils (C). The areas of the nerve terminal contacting the collagen lack a Schwann cell (S) and are indicated with
arrowheads. The basal lamina (BL) is indicated by an arrow. The nerve terminal contains mitochondria and many small clear vesicles.
Fibrocyte (F). Scale bar, 1 mm. (B) A neuromuscular terminal of a palisade ending in cat extraocular muscle. An ultrathin section
through a nerve terminal (T) establishing contact (arrow) on the muscle fiber (MF). The synaptic cleft is free from a basal lamina (BL).
Inset: line drawing of the region of interest. Scale bar, 1 mm (modified from Konakci et al., 2005).

origin then they would have cell bodies associated
with the oculomotor nuclei. Tozer and Sherrington
(1910) as well as Sas and Schab (1952) provided
evidence for their location in the oculomotor nerve
or nucleus, a result more compatible with either a
motor role for the palisade endings, or perhaps an
aberrant pathway for the afferent axons (Gentle
and Ruskell, 1997; Ruskell, 1999). The results of
other studies point to the trigeminal ganglion as
the location of palisade ending soma (Billig et al.,
1997), and imply a sensory function. The function
of palisade endings is at present not clearly
understood.
Golgi tendon organs
Golgi tendon organs have been reported in the
tendons of extraocular eye muscles of some
artiodactyls such as sheep, camel, pig, and calf
(Ruskell, 1990, 1999; Blumer et al., 2000), and very
rarely in monkey (Ruskell, 1979). They exhibit
structural features not seen in skeletal Golgi
tendon organs, several different types have been
described and are shown in Fig. 6. More specifically,
they have an enlarged capsular space and most
Golgi tendon organs contain up to three muscle
fibers. Such intracapsular muscle fibers are one
88

Fig. 6. Schematic drawings of different types of Golgi tendon organ found in sheep. (A) Type 1: contains exclusively collagen bundles.
(B) Type 2: three muscle fibers terminate inside the tendon organ. (C) Type 3: one muscle fiber traverses the tendon organ. (D) Type 4:
one muscle fiber terminates inside the tendon organ and another passes through it. C, capsule; N, nerve; COL, collagen; MF, muscle
fiber (modified from Blumer et al., 2000).

Fig. 7. Golgi tendon organ in the eye muscle of a cow. Ultrathin section through a nerve terminal (T) among the collagen bundles. The
terminal is filled with dark mitochondria and some smaller lighter vesicles are visible. Schwann cell (S), basal lamina (arrowhead).
Inset: line drawing of the region of interest (modified from Blumer et al., 2003).

special type of eye muscle fiber — the MIFs —
which are exclusive to eye muscles, and in this case
serve to adjust the sensitivity of the Golgi tendon
organ (Blumer et al., 2000). Of particular interest
in the context of this paper, is that all the Golgi
tendon organs lie in one specific layer of the eye
muscle, called the peripheral patch layer (Blumer
et al., 2000). The ultrastructural features of Golgi
tendon organs in eye muscles of artiodactyls are
illustrated in Fig. 7.

Fig. 8. Drawing of the development of skeletal Golgi tendon organs, adapted from Zelená and Soukup (1977). Palisade endings
resemble immature Golgi tendon organs at development stage P3.
The origin of palisade endings is unclear, but one
exciting suggestion comes from the work of Zelená
and Soukup (1977) on the development of Golgi
tendon organs, and is illustrated in Fig. 8. In their
study of Golgi tendon organs in rat skeletal muscle,
they found that at the embryological stage E21 a
nerve inserts between the aponeurosis and the at-
taching muscle fibers. At the postnatal stage P5 the
development of myelin around the nerve by
Schwann cells is accompanied by the growth of a
fibrous capsule, the nerve terminals begin to with-
draw from the muscle fibers into the tendon, and in
addition the immature MIFs become singly inner-
vated with a central endplate. The Golgi tendon
organ is fully developed at the stage of P14.
However, the immature Golgi tendon organ, at
day P3–5, where the nerve is attached to the mul-
tiply innervated muscle fibers, is strikingly similar
to the morphology of palisade endings. This led
Zelená and Soukup (1977) to suggest that palisa-
de endings may represent immature Golgi tendon
organs.
In summary, it seems possible that each eye muscle
layer has its own individual type of proprioceptors
(Fig. 9). If this hypothesis survives more intensive
scrutiny then it will certainly simplify the under-
standing of eye muscle proprioception. And an
important question to answer now is what factors
89
determine whether the proprioceptors occur and
persist in each layer, or not.
A possible role for palisade endings and the global
layer MIFs
Whether or not all these receptors provide a
proprioceptive input to the central nervous system
is not known. Palisade endings are associated with
the MIFs of the global layer, which insert via the
tendon onto the eyeball itself: thus the palisade
endings would be admirably suited to sensing eye
movements. If this is the case, and they function as
a giant ‘‘inverted muscle spindle’’ to use the words
of David A. Robinson, the MIF motoneurons
would be the equivalent of the g-innervation of a
muscle spindle, regulating the baseline activity.
The afferent signal could be used to adjust eye
alignment or calibrate space (Lewis et al., 2001;
Büttner-Ennever et al., 2003). Ultrastructural
studies of the eye muscles of patients with con-
genital strabismus showed that the innervation of
the myotendinous junction was abnormal in these
cases, and could conceivably contribute to the eye
misalignment (Domenici-Lombardo et al., 1992).
Given the close association of the global MIFs
with the palisade endings, it is of special interest to
90

Fig. 9. A schematic drawing of the location of sensory receptors in the extraocular eye showing that different receptors are associated
with a different muscle layers. The muscle spindles lie in and around the orbital layer, palisade endings in the global layer and Golgi
tendon organs (only present in artiodactyls) in the peripheral patch layer.

Fig. 10. Hypothetical proprioceptive pathways based on known connections: if proprioceptive signals are generated in the palisade
endings on multiply innervated extraocular muscle fibers (MIFs), the information may first relay in the spinal trigeminal nucleus (Sp
trig. n). From here axons project to the superior colliculus tier, which is closely interconnected to the central mesencephalic reticular
formation (cMRF), and the supraoculomotor area (SOA). The cMRF and SOA are direct premotor structures for the oculomotor
neurons of the MIFs.

understand if the MIF motoneurons function
as g-motoneurons. Recently, experiments were
conducted to determine the MIF motoneuron
location and premotor inputs. The motoneurons
of the global MIFs lie around the periphery of the
oculomotor trochlear and abducens nuclei, not
within the individual motoneuron subgroups, but
in slightly separate groups, namely the C-group,
the S-group, the trochlear cap, and the medial aspect
of the abducens nucleus, described in Chapter 4
(Büttner-Ennever et al., 2001). The premotor
inputs to the global MIF motoneurons were
investigated with transsynaptic retrograde tracers
that were confined to the distal MIF endplate
region of the muscles, distal to the central motor
endplate zone, and also distal to the termination of
the orbital layer (Büttner-Ennever et al., 2002).
The tracer did not pass back to the classical

premotor regions for eye movement control (e.g.,
paramedian pontine reticular formation (PPRF)
or the magnocellular vestibular nuclear neurons),
but that it was transported from the lateral rectus
MIF motoneurons retrogradely to vestibular areas
possibly associated with gaze-holding, and to
the mesencephalic reticular formation and the
supraoculomotor area. The latter two regions are
directly and intimately interconnected to the
superior colliculus (Chen and May, 2000), a
center of sensorimotor interaction for eye position
(Basso et al., 2000). Furthermore, the ascending
axons of the spinal trigeminal nucleus (Fig. 10)
that could carry putative proprioceptive signals
from the palisade endings, and project to the same
collicular layers that project to mesencephalic
reticular formation and the supraoculomotor
area (Harting and Van Lieshout, 1991; Mize,
1996; Waitzman et al., 2000). The possibility that
this circuit, and of course others including the
cerebellum, could subserve proprioception seems
possible from the neuroanatomical results, and is
put forward as a hypothesis in Fig. 10.
In conclusion, we have considered the evidence
for sensory innervation of eye muscles and for the
central pathways that may be involved in the
information processing. Some patterns in the or-
ganization of the muscle spindles, palisade endings,
and Golgi tendon organs with respect to different
muscle layers has been recognized, and may lead to
a clearer understanding of the factors involved in
their development (Büttner-Ennever et al., 2003).
The morphological results are still open to different
interpretations, but a sensory hypothesis fits more
easily with most physiological, clinical and neuro-
anatomical studies (Lewis and Zee, 1993). At
present it seems that palisade endings are a more
likely candidate than muscle spindles for a role in
proprioception, although this hypothesis is not fa-
vored by all of the authors. But a primary goal for
future experiments has to be the location of the
neuronal cell bodies of the receptors, and the de-
termination of the afferent pathway.
Acknowledgments
This research was supported by a grant from the
Deutsche Forschungsgemeinschaft (Ho 1639/4-1).
91
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