The Final Common Pathway in Postural

ControlDevelopmental Perspective
D. KERNELL
1
Department of Medical Physiology, University of Groningen, Bloemsingel 10, 9712 KZ Groningen, Netherlands
KERNELL, D. The nal common pathway in postural controldevelopmental perspective. NEUROSCI BIOBEHAV REV 22(4)479
484, 1998.A brief review is given concerning postural specialisations among mammalian muscle bres and motor units. Most skeletal
muscles contain a mixture of bres with different characteristics, and their slow-twitch (S) units are well-known to possess properties
suitable for postural tasks: they are highly fatigue-resistant, well equipped for oxidative metabolism, and their slowness makes them
energetically cheap in (semi-)isometric contractions. These features are adequately employed in motor behaviour owing to
characteristics of the associated motoneurones. In adult mammals, the way in which a muscle is used can inuence its proportion of
S units. This adjustment occurs within a restricted adaptive range which differs between muscles and animal species, presumably being
preset at an early age. In the course of early foetal development, part of the slow vs. fast differentiation of muscle bre properties can
take place independently of innervation. Once innervation has taken place, however, motoneurones inuence the differentiation in
various ways. On the whole, a well coordinated timing seems to exist between the early differentiation of central motor mechanisms and
of the peripheral machinery, largely causing the neuromuscular system to be/become ready for use when the brain needs it. 1998
Elsevier Science Ltd. All rights reserved.
Skeletal muscle Motoneurone Motor unit Posture Speed Fatigue resistance Plasticity Development
INTRODUCTION
IN GENERAL, the control of posture is necessarily strongly
linked with that of movement: dynamic motor actions can-
not be performed without (rst) stabilising sections of the
body that have to act as pivots for the moving parts. Further-
more, in behaving terrestrial animals there is also a perma-
nent ght against the force of gravity, which is opposed by
the continuous production of postural counter-force. Move-
ments and posture do, however, put partly contrasting
requirements on the nal common pathway in motor con-
trol, the motoneurones and their muscle bres. For the
muscles such requirements include the following.
1. In posture: nely graded contractions of weak to mod-
erate force, often of a (semi-)isometric nature. The
contractile duration may be very long; hence, energy
substrates should continuously be delivered from the
blood and a good capacity for oxidative metabolism
and an adequate capillary supply is essential.
2. In movements: rapidly regulated and brief (but often
intermittently repeated) contractions, with possibilities
available for the production of high force and power.
Hence, energy will often have to be rapidly mobilised
from internal stores (glycogen), sometimes under (semi-)
anaerobic conditions due to the temporary occlusion of
blood vessels.
Instead of having individual bres combining all the
necessary properties for these functional extremes, the con-
trasting muscular requirements in posture and movement
are largely taken care of by muscle bres with correspond-
ingly contrasting properties. In fact, there is a wide and
rather continuous range of variation in the contractile
requirements, from near-isometric postural contractions
lasting for hours (e.g. many antigravity muscles) to ballistic
contractions providing maximal acceleration of limbs (e.g.
in a jump). Correspondingly in individual muscles there is
also a wide and rather continuous range of variation in many
of the muscle bre properties. Still, it is descriptively
feasible and practical to subdivide this continuum into a
number of major groups, such as the slow (S) bres which
are optimised for postural use and the fast (F) ones which
are optimised for movements (comprising subvarieties with
different degrees of fatigue sensitivity). In this brief review,
neuromuscular function and differentiation will only be
discussed using the simple S vs. F dichotomy. The following
questions will be dealt with:
1. How S motoneurones and their muscle bres (i.e. S
muscle units) are optimised for postural functions.
2. How the percentage of S bres and units in individual
muscles may be made to vary in response to long-term
changes of adult muscle use.
Neuroscience and Biobehavioral Reviews, Vol. 22, No. 4, pp. 479484, 1998
1998 Elsevier Science Ltd. All rights reserved
Printed in Great Britain
0149-7634/98 $32.00 + .00
PII: S0149-7634(97)00033-X
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479
1
Tel.: 31-50-3632660; fax: 31-50-3632751; e-mail: d.kernell@med.rug.nl.
3. How postural aspects of the neuromuscular system
develop and differentiate in early life.
NEUROMUSCULAR SPECIALISATIONS AND POSTURAL NEEDS
A crucial aspect of posture is that it often has to be con-
tinued for a long time, i.e. a high degree of endurance is
absolutely essential. This property is optimised in the slow
and oxidative S bres to a remarkable degree compared with
F bres of the same muscle (for review and references see
(6,20,25)). The slow contractile speed itself contributes to the
high postural endurance because the maintenance of iso-
metric contractile force is metabolically cheaper in slow than
in fast bres (e.g. (10)). S bres (histochemically correspond-
ing to type I bres) may be identied and counted/measured
in histochemical preparations stained for myobrillar
ATPase. Muscles with marked postural functions have large
numbers of S bres. Muscles consisting only of S units are,
however, rare exceptions (e.g. cats soleus muscle); practi-
cally all skeletal muscles are of a mixed composition.
An appropriate employment of S units for posture, includ-
ing the adequate use of their potentially high endurance,
requires specialisations also in the neural component of
the nal common paththe motoneurones. In posture as
well as in movement, the central nervous system controls
force by (1) varying the number of active motoneurones
(recruitment gradation) and (2) varying the discharge
rate of already recruited units (rate gradation). The manner
in which these gradation procedures are used together is
important for optimising endurance in postural control (cf.
(2)). In this context, the differentiation of membrane proper-
ties between S and F motoneurones is important.
1. The intrinsic membrane properties of S motoneurones
give them a high electrical excitability (low current thresh-
old for activation, see (25)) which makes them easier to
activate synaptically than is the case for F motoneurones.
Partly for this reason, the relatively small-axoned S moto-
neurones are usually preferentially recruited in weak con-
tractions, including those used for postural control. This
corresponds to recruitment according to Hennemans
size principle (20); neuronal size itself does not, how-
ever, have a known causal role in this context.
2. Contractions can generally be better maintained at low
than at high relative force levels of the individual muscle
bres. Therefore, it is important for endurance that
steadily activated S motoneurones have properties that
make them capable of discharging regularly at rates for
which the twitches of their muscle bres hardly fuse;
such slow rates will occur when these motoneurones are
just barely recruited. This speed-match between mini-
mum ring rate and muscle unit contractile speed reects
a similarity between the duration of a muscle unit twitch
and the duration of the motoneuronal afterhyperpolarisa-
tion (AHP; (1,24)). Owing to the asynchronous activity
of different motoneurones in the same pool, the sum of
markedly unfused contractions in several recruited S
units may result in a relatively steady muscle force.
ADULT NEUROMUSCULAR PLASTICITY
It is well-known that the properties of skeletal muscles
are modiable by training (sport, rehabilitation, etc.).
Recruitment according to the size principle automatically
leads to different levels (and patterns) of activity for F vs. S
muscle units. To what extent are the functional differences
between these brands of units a long-term consequence of
their different levels of natural training?
If an innervated fast-mixed muscle is subjected to exten-
sive daily amounts (about 5% or more of total time) of
electrical activation over several weeks, it becomes slower,
more fatigue-resistant and, somewhat paradoxically, its
muscle bres also may become thinner and weaker (e.g.
(4,12,13,26,28,37); for reviews and further references see
(16,25)). The strengthening of normal muscles seems to
require smaller amounts of daily training, including con-
tractions of great force. The effects on the various contrac-
tile properties depend, in different ways, on the stimulation
parameters. The total daily duration of activation is impor-
tant for all effects. High pulse rates (i.e. strong evoked
forces) have generally been found to be benecial for the
maintenance of muscle strength. Pulse rates have not,
however, been found to be of critical importance for the
effect of chronic stimulation on the speed of mixed-fast
muscles (cf. (27,28)). Following cessation of chronic
stimulation, muscle alterations revert back toward normal.
This reversion happens more quickly for the slowed iso-
metric speed and the decreased muscle force than for the
increased fatigue resistance (4,27).
It is clear that many of the striking consequences of
chronic activation on muscle properties are expressed via
effects on the machinery for gene transcription and RNA-
mediated protein synthesis. It is still unknown, however,
how motoneuronal and contractile activity is linked to
such effects and which intramuscular messenger molecules
may be involved. Several of the effects can also be produced
by direct electrical stimulation of denervated muscle bres
(e.g. (21,30,43)); thus, these long-term effects do, at least
partly, come about as a direct consequence of the evoked
muscle bre activity. It is still unknown what the additional
role might be of an activity-dependent synaptic release of
particular molecules at the end-plate.
There is much evidence indicating that, in the adult
animal, muscle bres are pre-specied with regard to the
range within which their properties may be readily changed
by alterations of use (adaptive range). Thus, when com-
paring the long-term consequences of chronic stimulation
between different experiments it has repeatedly been noted
that the amount of effect can be very different for different
species of animals (e.g. (38)) and for different muscles in the
same animal (e.g. (43)). Conversely, a marked decrease in
the amount of normal daily activity does not necessarily
cause marked changes to take place in physiological and
histochemical muscle bre properties (e.g. (12,13,35)).
Re-innervation experiments have shown that, although
motoneurones may re-specify properties of many of the
muscle bres, biochemical characteristics of some bres are
markedly resistant to such neuronal inuence ((40), cf.
(22)).
Besides long-term inuences from motoneurones on
muscle bres (partly caused via motoneuronal effects on
muscle bre activity), there are also differentiating mechan-
isms working in the opposite direction. Thus, under certain
conditions slow type-I bres of adult animals even seem
capable of changing the properties of re-innervating moto-
neurones from fast to slow with regard to their AHP and
480 KERNELL
input resistance (for review see (31)). The molecular
mechanisms involved in such actions are still unknown.
Also in adult animals, motoneurone-independent
mechanisms and agents may operate to change the distribu-
tion of muscle bre properties within mixed muscles. A
well-known example is thyroid hormone, which also has
effects on denervated muscles (34), tending to down-
regulate the expression of type-I myosin and upregulate
that of certain kinds of type-II myosin. In addition, muscle
bulk may, of course, be markedly inuenced by other
hormones (e.g. growth hormone, anabolic steroids).
NEUROMUSCULAR DEVELOPMENT
General course of events
Mature muscle bres arise from myotubes which come
about from the fusion of mononuclear myoblasts. In normal
development this process typically takes place in two main
phases (for review and references see (23)):
1. rst the primary myotubes arise, in the rat from at least
about foetal day 12 (E12);
2. thereafter, secondary myotubes emerge using the
primary generation of cells as a scaffolding. This
process continues for varying times, in some species
and muscles until well after birth.
In man, much of the myotube and myobre formation
takes place in gestational weeks 719; already during this
period different immunocytochemical bre types can be
distinguished. Different histochemical types start appearing
around weeks 1617 (quadriceps femoris, myosin ATPase;
for further information and references, see ref. (7)).
Motoneurones belong to the earliest nerve cells to appear
within the spinal cord and their axons reach the developing
muscle at the time of formation of the primary myotubes.
About 50% of all the initial motoneurones ultimately die; in
rat hindlimb pools, this process of cell death is completed
prior to birth (23). Surviving neurones are thought to prot
from benecial retrograde effects from their target cells.
The initial innervation of myotubes and muscle bres is
such that each muscle cell receives terminals from several
motoneurones. In hindlimbs of rats, this situation persists
until about 23 weeks postnatally. For instance, after about
postnatal day 15 (P15) most soleus muscle bres receive
innervation from only one motoneurone, i.e. typically the
motor units no longer overlap.
One of the earliest physiological observations on mus-
cular development concerned the early time course of
changes of isometric speed. In rats as well as cats, the
muscles that later develop into slow (typically soleus)
and those ultimately becoming predominantly fast (the
majority of mixed muscles) have a similarly slow isometric
twitch at birth (e.g. (5,8)). Both sets of muscles rapidly
become faster during the initial postnatal weeks. Subse-
quently, the two kinds of muscle deviate: soleus starts
slowing down again while the fast muscles remain fast.
The changes of isometric twitch speed probably primarily
reect changes in the calcium kinetics associated with bre
activation and say little about alterations in the speed of
shortening. When directly measured, the maximum speed
of shortening has also been found to increase during the
early postnatal period; in the rat this increase was, however,
not seen in slow but only in fast muscle (8). Myosin
composition runs through a complex sequence of changes
(e.g. (36)), including embryonic and neonatal myosin
heavy-chain isoforms that are normally not found in adult
muscle bres.
Role of motoneurones for the (early) differentiation of
muscle bre properties
There is now much evidence that (part of) the differentia-
tion of muscle bres into different biochemical categories or
types can take place independently of the motoneurones.
Also under aneural conditions different bres will, for
instance, express different nal brands of myosin (rats:
(9,22); chicken: (32)). Part of this process is related to the
generations of initial myotubes, the rst generation being
preferentially slow and the second one initially fast (but
adjustable in later life). Motoneuronal innervation is thought
to be important for the appearance and ripening of the
secondary bres. It is largely unknown which other mechan-
isms may be responsible for the early differentiation
sequence; thyroid hormone plays a role ((36)), at least for
the speed at which changes occur ((11)). It is still unknown
how the adaptive ranges of the future adult muscle bres
are set.
Ingrowing motoneurones apparently recognise different
classes of emerging muscle bres such that, ultimately,
functionally homogeneous muscle units may arise because
of an early matching based on cell recognition ((23)). Thus,
in the early postnatal period of polyneuronal innervation,
bres within overlapping muscle units all tend to belong to
the same type ((39)).
In the early postnatal period the regression of poly-
neuronal innervation is critically dependent on the presence
of motoneuronal activity (for review see (23,33)). Activity
also plays a complex role in the competition between
different motoneurones for keeping a given muscle bre.
In the postnatal development of contractile muscle prop-
erties, the long-lasting tonic discharges of slow moto-
neurones apparently exert a slowing effect on their muscle
bres. The secondary slowing of isometric contraction in
the cats soleus muscle did not take place when the animals
were made less tonically active by high-lumbar transection
of the spinal cord ((5)). Similarly, in rats the percentage of
slow postural bres in the soleus gradually increases as the
animal grows older and heavier ((29)). Thus, in these cases,
postural needs apparently serve to adjust the properties of a
markedly postural muscle already in early life. Within the
limits somehow set by adaptive ranges, such adjustments
remain possible throughout adult life (see above).
Does the rate of early neuromuscular differentiation
constitute a bottleneck in the development of motor
behaviour?
In many species of animals, the neuromuscular properties
have not yet reached their adult level of specialisation at
birth. Most of the available knowledge concerns rats and
cats who both are altricial animals, being relatively
helpless for some time after birth (as is also, obviously,
the case for humans). The late development of their motor
behaviour is probably, to a dominating extent, reecting the
rate of development of the central neuronal mechanisms
NEUROMUSCULAR DIFFERENTIATION AND POSTURE 481
responsible for driving the spinal motoneurones. Still, this
development seems to happen with a relatively parallel time
course for the central mechanisms as for the neuromuscular
system. Hence, it is of some interest to consider in which
respects an immature neuromuscular system might be a
limiting factor in the timing of appearance of adequate pos-
tural behaviour. Lifting the body off the ground during loco-
motion might be considered a postural mile stone. For rats,
this maturation of locomotory posture takes place from
about postnatal days P1011 ((42); see also (15,17)); for
cats, a secure weight-bearing posture is achieved at around
P21 ((3)). Was this milestone reached at a given time
because only then had the neuromuscular properties
become ready for adequate postural use? Or were the
required neuromuscular properties already there, waiting
for the brain to put them to work? Below, such questions
will be discussed in relation to a small selection of all the
potential problems involved.
Tonic activity in motoneurones
At around P10P12 the motor activity of postural
muscles (e.g. soleus) in the rat starts to change from being
dominated by brief bursts of phasic activity to also show-
ing long-lasting tonic discharges, as would be needed for
postural stabilisation ((33)). There is, however, no evidence
that the generally phasic behaviour of neurones in younger
animals depends on them being intrinsically incapable of
delivering a long-lasting repetitive ring; such tonic
discharges have been evoked with injected currents in
motoneurones of rats at day P8 or earlier ((14)).
Speed-matching between motoneurone and muscle
If the AHPs of neonatal motoneurones were as brief as
those of adults, then they would not be well matched to the
prolonged neonatal twitch durations; the minimum steady
discharge rates of neonatal motoneurones would then be too
high for the production of well maintained contractions (i.e.
too much twitch fusion). This highly unmatched situation
apparently does not appear because not only the twitches but
also the AHPs are longer in neonatal than in adult rats. In the
data of ref. (14) (calculated from their table 1), the average
(SD) AHP duration of unspecied neonatal lumbar moto-
neurones was 120 26 ms (n 33) and, during the period
covered by these measurements (P3P12), there was no
signicant correlation with age (r 0.03, n 33). In adult
rats, the average AHP duration for gastrocnemius medialis
and tibialis anterior motoneurones is 54 14 ms (n 125),
which is signicantly shorter than the neonatal value (P p
0.001; adult data from ref. (1)). Thus, there is apparently a
general tendency also for a certain degree of AHP vs. twitch
duration matching in neonatal animals. However, it is still
unknown how well this match is set and maintained
throughout the postnatal period for the slow postural units.
In the cat, an evident co-variation between twitch speed and
AHP duration is present from about 6 weeks of age, not just
after birth ((19)). In predominantly fast rat muscles, twitch
duration seems to speed up by a factor of about 4 from birth
to adulthood (see illustrations of (8)); this change appears
greater than the average shortening of AHP duration (the
data above suggest an AHP shortening by about 120/54
2.2). However, during the rst couple of weeks, the relation-
ship between twitch and AHP duration will quickly readjust
itself toward more adult-like conditions because in this
initial period there is already a marked speeding-up of the
twitch ((8)), without as yet any simultaneous shortening of
the AHP ((14); cf. data from cat in (19)). Such a sequence of
events (twitch shortening prior to AHP shortening) would
be consistent with the presence of retrograde speed-setting
effects of muscle bres onto their motoneurones (cf. (31)).
Multiply innervated units
Even though multiply innervated units may be function-
ally relatively homogeneous ((39)), the state of poly-
neuronal innervation would be highly undesirable in
postural functions. In centrally evoked activity, endurance
would be endangered by using single muscle bres at too
high levels of contractile force, such as those caused by the
combined effects of slow but asynchronous discharges from
several innervating motoneurones. Hence, it seems of direct
relevance that, in the rat, the gradual disappearance of
polyneuronal innervation of soleus (P9P16; (23)) almost
precisely overlaps with the period of gradual development
of locomotory posture (P11P15; (42)).
Development of fatigue resistance
The fatigue resistance of developing hindlimb muscles
has not often been directly measured by methods such as
those regularly employed in adult muscle, using electrical
stimulation of the muscle nerve for standardised fatigue
tests ((6)). Some such data are available for the cat,
indicating that both future slow and fast muscles have
a high fatigue resistance initially (measured from postnatal
day P6P9; (18)). Thus, postural muscles apparently do
not need (much) postnatal activity (training) to acquire
their normally high degree of fatigue resistance. In the rst
few postnatal weeks of kittens, endurance remains high for
the postural soleus muscle while the fast-mixed tibialis
anterior becomes gradually more sensitive to fatigue (18).
Force?
One factor of crucial importance for the postural (anti-
gravity) use of neonatal limb muscles concerns their capa-
city for generating sufcient force (torque) in long-lasting
contractions, i.e. in contractions weak enough not to block
circulation or otherwise compromise endurance. Whether
an immaturity of force-production is a limiting factor of
importance for the timing of the early appearance of
motor behaviour is still unknown. Providing an answer to
this question is not a simple task; extensive biomechanical
measurements and calculations for all the relevant muscles,
joints and moment-arms would be required.
EPILOGUE
The data reviewed in Section 4 suggest that there is, on
the whole, a well coordinated timing between the early
differentiation of the central motor mechanisms and the
peripheral machinery, largely causing the neuromuscular
system to be/become ready for use when the brain needs it.
This is further illustrated by comparisons between the time
course of neuromuscular changes in altricial (e.g. cats, rats;
helpless at birth) and precocial animals (e.g. sheep; can walk
from birth). For instance, the early speeding-up of the
isometric twitch of fast muscles, which occurs during the
482 KERNELL
initial postnatal weeks in cats and rats, takes place well
before birth in the precocial sheep (41). In these latter
investigations, there was no evidence indicating that foetal
movements were of importance for foetal muscle differen-
tiation. Hence, this is yet another observation stressing the
largely preprogrammed nature of early neuromuscular
development. The role of motoneuronal activity and train-
ing seems typically that of producing auxiliary (but poten-
tially very important) adjustments rather than being a
primary shaping force.
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