PROFESSOR DR ROLAND BLUMER
Proprioception and
palisade endings
Professor Dr Roland Blumer is challenging theories about palisade endings and their role
in proprioception, the ability to sense the relative position of body parts. Here, he discusses
the possibility that these nerve endings possess motor function and the potential to change
procedures in eye surgery
Can you explain what palisade endings
are, where they can be found and
their unique characteristics?
Palisade endings are unique nerve terminals
found exclusively in the eye muscles
of mammals. They are located at the
connections of the muscle with the tendon
and are found on the tip of a single muscle
fibre. There, they form a dense structure of
mostly parallel arranged axons and axonal
terminals. The name ‘palisade ending’ comes
from the similarity of this structure with a
palisade, a construction made mainly of wood
consisting of parallel arranged boards fixed
into the ground.
Why are these structures of particular
interest to you?
Palisade endings were detected in the eye
muscles of mammals over 100 years ago.
They were thought to be sensory receptors
providing the brain with eye position signals.
Our detailed structural analyses, however,
have revealed that palisade endings have
some features of a motor nerve terminal,
putting their sensory function into question.
For that reason, we have decided to
analyse the molecular patterns and central
connections of palisade endings.
What is proprioception? How does it
correlate with the ability to see in mammals?
Proprioception is the ability to register body
position. In terms of vision, proprioception
provides information about the position and
movement of the eyes. This is a prerequisite
for determining the direction of gaze and
the relationship of the organism to its
environment. Moreover, proprioception in
eye muscles is thought to be important
for the development of normal binocular
40
INTERNATIONAL INNOVATION
vision. In limb muscles, proprioceptive
signals come from special sensory receptors
(proprioceptors). We were surprised to learn
that classical proprioceptors are absent in
the eye muscles of most mammals, with
the exception of even-toed ungulates such
as pigs. However, palisade endings have
been found in all species investigated, and
it has been proposed that they might be the
principal proprioceptor in the eye muscles.
Findings from your team have reopened
debate around the function of palisade
endings. Could you explain these discoveries
and their significance?
Since their characterisation, there has been
an ongoing debate about the function of
palisade endings. The century-long consensus
is that they are putative proprioceptors.
Our molecular analyses have shown that
palisade endings contain acetylcholine,
which is the typical neurotransmitter of
motor terminals. In two consecutive studies,
which were conducted in collaboration
with Professors Angel Pastor and Paul
May, we determined that the origin of
palisade endings lies in the motor nuclei
of the brain. Molecular and connectional
findings have put into question whether
palisade endings are pure proprioceptors.
Can you elaborate on the origin of palisade
endings in the brain? To what extent have
you been able to pinpoint this?
There is some discrepancy concerning
the origin of palisade endings in the brain.
A neuronal tracing experiment revealed
evidence that the cell bodies of palisade
endings lie in the sensory trigeminal ganglion,
while a degeneration experiment indicated
that the cell bodies of palisade endings are
found in the motor nuclei of the eye muscles.
We therefore re-analysed the source of
palisade endings. Following tracer injection
into the eye muscle motor nuclei, we found
tracer labelled palisade endings in the eye
muscles. In a counter experiment, we found
no cholinergic elements in the trigeminal
ganglion. These findings exclude the idea
that palisade endings receive innervation
from this sensory ganglion. Neuronal tracing
experiments complement molecular findings,
indicating that palisade endings are more
likely to be motor structures/effector organs
than sensory organs.
How could your research be translated for
clinical application?
Palisade endings are located in the target
region of strabismus surgery. In many surgical
procedures to treat the condition, distal
parts of the eye muscles containing palisade
endings are removed. Knowledge of the
function of palisade endings might enhance
our understanding of conditions involving
binocular dysfunction like strabismus, and
thus influence surgical procedures.
Insightful advancements
Investigators at the Medical University of Vienna, Austria, are challenging the time-honoured
belief that palisade endings are the principal proprioceptors in the eye muscles. Instead, they have
shown that these nerve terminals respond to acetylcholine, the neurotransmitter responsible for
muscle contraction, and that the origin of palisade endings lies in motor nuclei of the brain
BEYOND THE FIVE familiar senses, the
human body possesses additional ones
that are crucial to the activities of everyday
life. For instance, exteroception enables
humans to perceive the outside world,
while interoception is responsible for the
recognition of hunger. Proprioception,
however, is perhaps more complex,
describing awareness of the relative
position of parts of the body.
The brain can sense the body, as well as its
position and movement in space; this ability,
unconsciously mediated by the cerebellum,
is what allows humans to perform even the
simplest tasks, such as closing their eyes
and touching their nose. These interactions
rely on special sense organs in muscles
called proprioceptors, which continuously
inform the brain to coordinate movement.
Proprioception is particularly important
for the eyes, the most mobile organs in
the body, as knowing where the eyes are
pointing is required for vision. Proprioceptive
input from the eye sends a signal to
the brain and enables individuals to
determine where objects are located in
space. This is the foundation of a range
of activities – those fundamental, such
as reaching out for an object, or more
complex, such as driving a vehicle.
Palisade endings, unique structures found
on the end of muscle fibres in the eyes,
are thought to be the organs’ primary
proprioceptors. However, this is the subject
of intense debate, as new evidence suggests
they may in fact have a motor function rather
than a sensory one (ie. they carry signals
from the brain to muscles, as opposed to
transmitting sensory information back to
the brain).
A CONTENTIOUS HISTORY
Palisade endings were first described in
1906. Further experiments identified these
nerve endings in every species investigated,
from rats to monkeys and man. These
unique structures are found exclusively
in eye muscles, located at the junction
between the muscle and the tendon.
Although evidence for their function is
severely lacking, the current consensus is
that these structures are sensory receptors,
which likely represent the principal
proprioceptor in mammalian eye muscles.
Challenging this assumption is Professor Dr
Roland Blumer from the Medical University
of Vienna’s Center for Anatomy and Cell
www.internationalinnovation.com
41
Biology, who has dedicated the past 20
years of his research to understanding the
proprioception of mammalian eye muscles.
In the last decade, he has specifically
focused on palisade endings.
Showing two palisade endings labelled with antibodies
against neurofilament (red) and choline acetyl
transferase (green). Double labelled structures appear
in yellow. The muscle fibres are in blue.
Blumer’s initial investigations into the
structure of palisade endings revealed
an interesting finding; he discovered an
abundance of clear vesicles, typically
used to store neurotransmitters, in their
peripheral nerve terminals. Intrigued, his
team went on to investigate the properties
of these vesicles. They applied three
different markers of acetylcholine, a
neurotransmitter typically found in motor
terminals. All the markers were positive,
indicating that palisade endings are
cholinergic, similar to the motor endplates
of neuromuscular junctions, which connect
the nervous system to the muscular system
by causing muscle contractions.
INTELLIGENCE
EFFECTOR FUNCTION OF PALISADE ENDINGS
Blumer’s molecular and
OBJECTIVE
neuronal tracing findings
To analyse the molecular pattern and central
connections of palisade endings to gain further insight
into their function.
KEY COLLABORATORS
Professor Angel Pastor, University of Seville, Spain
Professor Paul May, University of Mississippi Medical
Center, USA
FUNDING
Austrian Science Fund (FWF):
Projects P 15478; P 20881-B09
CONTACT
Professor Dr Roland Blumer
Center for Anatomy and Cell Biology
Integrative Morphology Group
Medical University of Vienna
1090, Vienna
Austria
T +43 140 1603 7554
E [email protected]
PROFESSOR DR ROLAND
BLUMER completed his studies
in biology in 1992, after which
he began work at the Medical
University of Vienna. In his
research, Blumer focuses on the proprioceptive
innervation of eye muscles in various mammals
including humans. He is currently Associate Professor
in the Center for Anatomy and Cell Biology.
strongly suggest that palisade
endings are effector nerves
The results, which showed that palisade
endings can synthesise acetylcholine,
strongly indicate that these eye musclespecific organs have an effector role (ie.
they activate muscle) – putting into question
the idea that palisade endings are pure
proprioceptors. These findings have reopened
the debate about their function.
AN UNEXPECTED DISCOVERY
Building on these extraordinary discoveries,
Blumer embarked on a collaboration with
two additional experts in the field: Professor
Angel Pastor from the University of Seville,
Spain, and Professor Paul May of the
University of Mississippi Medical Center, USA.
Together, they set out to determine where
in the brain palisade endings emerge from,
as this is key to identifying their function.
Having shown that palisade endings are
cholinergic, they posited that their cell bodies
would lie in the motor nuclei that control the
eye muscles. To prove this, the researchers
injected a neuronal tracer into the motor
nuclei of the eye muscles. Sure enough,
tracer-labelled palisade endings were
observed in the eye muscles, indicating that
the cell bodies of these nerve endings do in
fact lie in the motor nuclei.
In a follow-up study published in The
Journal of Neuroscience, the researchers
combined the use of a tracer with
42
INTERNATIONAL INNOVATION
immunohistochemistry, a technique that
uses antibodies to detect proteins. They used
the technique to search for cell bodies in the
trigeminal ganglion, the nerve responsible
for facial sensation. “No cholinergic elements
were found there,” explains Blumer. This put
an end to the concept that palisade endings
receive cholinergic trigeminal projections,
and again called into question their
proprioceptive function.
Taken together, Blumer’s molecular and
neuronal tracing findings strongly suggest
that palisade endings are effector nerves
– those that carry nerve impulses away
from the central nervous system (CNS) to
effectors (in this case, the muscles) – rather
than sensory neurons, which transmit
sensory information to the CNS.
AN ONGOING DEBATE
While these findings are extremely
convincing, the debate is far from closed.
Recent results emerging from Germany
show the cell bodies of palisade endings
to be shaped like a spindle, resembling
sensory cells. They also reveal that they
are located near the Edinger-Westphal
nucleus, which contains the neurons that
are responsible for the near response. While
the authors did confirm Blumer’s finding
that palisade endings originate in the motor
nuclei of the eye muscles, they suggest
that palisade endings may also possess
a sensory function and participate in the
adjustment of the eye to close range vision.
Thus, the debate about the function of
palisade endings continues to flourish.
While there is no option but to interpret
their molecular characteristics as motor
structures, a functional basis for this
definition remains elusive.
FUTURE IMPLICATIONS
Indeed, a great deal of work remains to
be accomplished in the field. Though
Blumer has emphasised the likelihood that
these nerve endings release acetylcholine
on excitation, a receptor for this
neurotransmitter has not yet been identified,
and the effect of acetylcholine on the tendon
remains unknown. “Physiological and
further cell biological investigations have
to be undertaken to identify the function of
palisade endings,” he elaborates.
While the question remains open, the
achievements of Blumer and his team
should not be understated. They have
generated fundamental new anatomical
insights with important clinical implications.
“As palisade endings are found in
human eye muscles, our findings will
be of particular interest to surgeons,”
Blumer concludes.