J Appl Physiol 101: 1228 –1236, 2006;
doi:10.1152/japplphysiol.00482.2006.
Invited Review
HIGHLIGHTED TOPIC
Neural Changes Associated with Training
Effects of exercise training on ␣-motoneurons
P. Gardiner,1,2 Y. Dai,1 and C. J. Heckman3
1
Spinal Cord Research Center, Department of Physiology, and 2Health, Leisure and Human Performance
Research Institute, University of Manitoba, Winnipeg, Manitoba, Canada; and 3Departments of
Physiology and Physical Medicine and Rehabilitation, Northwestern University, Evanston, Illinois
Gardiner, P., Y. Dai, and C. J. Heckman. Effects of exercise training on ␣-motoneurons. J Appl Physiol 101: 1228 –1236, 2006. doi:10.1152/japplphysiol.00482.2006.—
Evidence is presented that one locus of adaptation in the “neural adaptations to
training” is at the level of the ␣-motoneurons. With increased voluntary activity,
these neurons show evidence of dendrite restructuring, increased protein synthesis,
increased axon transport of proteins, enhanced neuromuscular transmission dynamics, and changes in electrophysiological properties. The latter include hyperpolarization of the resting membrane potential and voltage threshold, increased rate of
action potential development, and increased amplitude of the afterhyperpolarization
following the action potential. Many of these changes demonstrate intensity-related
adaptations and are in the opposite direction under conditions in which chronic
activity is reduced. A five-compartment model of rat motoneurons that innervate
fast and slow muscle fibers (termed “fast” and “slow” motoneurons in this paper),
including 10 active ion conductances, was used to attempt to reproduce exercise
training-induced adaptations in electrophysiological properties. The results suggest
that adaptations in ␣-motoneurons with exercise training may involve alterations in ion conductances, which may, in turn, include changes in the gene
expression of the ion channel subunits, which underlie these conductances.
Interestingly, the acute neuromodulatory effects of monoamines on motoneuron
properties, which would be a factor during acute exercise as these monoaminergic systems are activated, appear to be in the opposite direction to changes
measured in endurance-trained motoneurons that are at rest. It may be that
regular increases in motoneuronal excitability during exercise via these monoaminergic systems in fact render the motoneurons less excitable when at rest.
More research is required to establish the relationships between exercise training,
resting and exercise motoneuron excitability, ion channel modulation, and the
effects of neuromodulators.
spinal cord; modeling; neuromodulation; electrophysiology
␣-MOTONEURONS ARE KNOWN to change their properties under a
number of conditions. Adaptations in ␣-motoneuron properties
occur during development (3), following spinal cord injury (11,
43), axotomy (4), blockade of action potentials along its axon
(18, 20), and treatment with various trophic factors (42, 69,
71). These changes include changes in properties that would be
expected to alter the ways in which neurons, and neuronal
circuits, translate and transfer excitation patterns into trains of
action potentials at the end organ. There is a significant volume
of evidence that the nervous system responds to increased
physical activity by changes in its properties (generally referred to as “neural adaptations to training”), although the
exact loci of these changes have not been established. Evidence
for neural adaptation to training would be strengthened considerably with evidence of adaptations at the single-neuron
Address for reprint requests and other correspondence: P. Gardiner, Dept. of
Physiology, Univ. of Manitoba, 730 William Ave., Winnipeg, Manitoba,
Canada R3E 3J7 (e-mail: [email protected]).
1228
level, as has been done in the case of learning. There is some
evidence, for example, that voluntary exercise increases dendritic complexity and spine density in rat dentate gyrus, although any functionally significant contribution to performance is not apparent (28). In this paper, we summarize our
current knowledge of exercise training-induced adaptations
occurring at the level of a neuron, which is in the final common
motor pathway, the ␣-motoneuron. Known adaptations to
␣-motoneurons in response to endurance-type training are
summarized in Fig. 1.
MORPHOLOGY OF THE SOMA, DENDRITES, AND AXONS
A significant change in motoneuronal morphology, including a change in size or in dendritic number, might herald a
change in functional properties. For example, a change from
“fast” to “slow” motoneurons, to parallel the change in muscle
fibers that occur with intense endurance training, might express
itself as an overall decrease on soma size, increased number of
stem dendrites, and a decrease in axon diameters in the periph-
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EFFECTS OF EXERCISE TRAINING ON ␣-MOTONEURONS
Fig. 1. Sites of exercise training-induced adaptations in ␣-motoneurons and
possible mechanisms. 1 ⫽ increased dendritic arbor; 2 ⫽ increased protein
synthesis, altered gene expression; 3 ⫽ altered ion conductances in soma and
initial segment, and perhaps dendrites; 4 ⫽ increased axon transport of
maintenance proteins, neurotrophins and receptors, and metabolic signals from
muscles; 5 ⫽ enhanced neuromuscular transmission efficacy.
eral nerve. Early reports on changes in axon diameters in
peripheral nerves have shown both increases (29, 60) and
decreases (5, 58), with much variability in findings attributable
to different species and intensities and types of exercise. With
respect to volume of the soma, findings generally indicate that
relatively few changes occur as a result of increases, as well as
decreases, in chronic neuromuscular activity (45, 61). One
study reported a modest (14%) but significant increase in
average diameter rat soleus motoneurons following endurance
training (53). A more recent electrophysiological study reported that estimated cell capacitance, an index of cell size,
was significantly increased for high-threshold fast motoneurons following intense endurance training (10). In contrast to
findings at the level of soma and axons, there appears to be an
effect of increased activity on dendrites. Lumbar motoneurons
of rats subjected to increased activity in voluntary exercise
wheels for 5 days had total dendritic arbors that were slightly
yet significantly larger, with larger arbors per dendrite (34).
Overall, the available literature suggests that changes occurring
in motoneuronal morphology with increased activity, if any,
are minor (with the exception of changes at the nerve terminal,
see below), although the demonstration of dendritic arbor
morphology may prove functionally significant with further
study.
NEUROMUSCULAR JUNCTION
Motoneuron adaptations also include the dynamics at the site
of interaction with its end organ, muscle, at the neuromuscular
junction. Endurance training appears to increase nerve terminal
branching at the neuromuscular junction (6, 25), although
results are equivocal (68). The functional significance of this
increased complexity at the neuromuscular junction, other than
the demonstration that motoneurons are responsive to increased activity, has not yet been elucidated. What does appear
to be consistent is the increased synaptic efficacy due to
enhanced neurotransmitter release that occurs with increased
activity (7, 24, 27). The increased safety factor and decreased
likelihood that neuromuscular propagation is impaired during
sustained activation of the neuromuscular junction appear to be
consistent with a strengthening of the neuromuscular apparatus
as a whole to offset fatigue. It is interesting to note that, while
this change is presynaptic, the muscle fiber responds by
strengthening the synapse in the form of increased acetylcholinesterase content (38) and acetylcholine receptor number
J Appl Physiol • VOL
1229
(23). Most likely a significant proportion of these changes is
supported by increased motoneuronal synthesis, axon transport, and secretion of trophic substances that influence transcription of subsynaptic myonuclei (see next section, BIOCHEMISTRY/METABOLISM).
The mechanism by which these neuromuscular junction
changes occur has been elucidated to some degree by experiments with crayfish (51). In crayfish neuromuscular junctions,
14 days of electrical stimulation produce an adaptation in
neuromuscular transmission (smaller decrease in end-plate
potential amplitude during sustained excitation) similar to that
found following endurance training, which is independent of
transmitter release and muscle fiber contraction and is evoked
by depolarization of the neuron alone (51). It appears that
metabolic events in the motoneuron soma related to depolarization produce this change in synaptic efficacy that occurs
with increased usage.
BIOCHEMISTRY/METABOLISM
Contrary to the lack of evidence of significant morphological
adaptations in motoneurons to increased activity, several indexes of the metabolic state of motoneurons are altered. Motoneurons of treadmill-trained rats possess nucleoli that are
increased in area and surrounded by basophilic particles and
have an increased staining intensity for glucose-6-phosphate
dehydrogenase, suggesting increased protein synthesis (30,
35). Trained motoneurons appear to possess the capability to
transport larger amounts of protein in their axons, in both
orthograde and retrograde directions (21, 48 –50). This transport is most likely important for the delivery of substances to
and from the periphery that are important for adaptation of the
motor unit as a whole. For example, the synaptosome-associated protein SNAP25, an important protein for docking of the
synaptic vesicle to the presynaptic membrane, is selectively
transported in higher quantities in axons of trained motoneurons (50).
Some proteins are present in higher quantities in trained
motoneurons. The enzyme malic dehydrogenase and the trophic factor calcitonin gene-related peptide are present in higher
amounts in the somata of trained motoneurons (35, 36). It
seems that the increased malic dehydrogenase, which exists in
mitochondrial and cytoplasmic isoforms, does not indicate an
increased mitochondrial content, since the mitochondrial enzyme succinic dehydrogenase (SDH) is not responsive to
endurance training or even decreased usage (53, 61). Although
SDH activity appears to vary inversely with soma size (26, 45,
63), the functional significance of this relationship has yet to be
determined. The lack of responsiveness of this enzyme to
variations in chronic activity, which is contrary to the relationship seen in muscle, probably indicates the lack of stress to the
mitochondrial energy-producing system that increased activity
imposes. It is worth noting that electrical stimulation of motor
axons for 50% of the total time per day for 8 wk in cats also
failed to evoke changes in SDH measured in somata, despite
dramatic changes in the same enzyme in the stimulated muscles. Since the motoneurons in that study were deprived of
peripheral afferent input, and thus action potential development was antidromic during the chronic stimulation, one can
conclude that the number of action potentials per day generated
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EFFECTS OF EXERCISE TRAINING ON ␣-MOTONEURONS
by a motoneuron (calculated from stimulation frequency and
time and pattern of stimulation) does not constitute a metabolic
stressor significant enough to evoke a mitochondrial enzyme
response. Similar conclusions were arrived at by Jasmin et al.
(48), who found that increased orthograde axon transport did
not occur with swimming training, despite the fact that weightsupported running training, which did result in an adaptive
response, involved approximately one-half of the total number
of extra action potentials per day.
The rate of regeneration and sprouting in response to a given
stimulus has been used experimentally to determine the effects
of activity on motoneuron metabolism, since these events
involve alterations in protein synthesis and axon transport.
Endurance-trained motoneurons appear to sprout more robustly
when given the stimulus (i.e., signals emanating from denervated fibers following partial denervation) to do so (31).
However, sprouting and regeneration capacities are reduced
when chronic activity is increased during the regenerative/
reinnervation process (33, 62).
More recently, emphasis has been placed on possible activity-mediated neurotrophin effects on motoneurons, since the
repeated demonstrations of exercise-induced increased neurotrophin expression in hippocampus (54). In hippocampus,
brain-derived neurotrophic factor (BDNF) increases are important for synaptic plasticity, learning, and memory (67). Hippocampal BDNF also increases robustly with exercise, and
exercised animals show enhanced cognitive function because
of this (67). BDNF regulates the mRNA levels of itself, its
receptor trkB, the transcription factor cyclic AMP-responsive
element binding protein, and synapsin I, which affects synaptic
transmission. These changes in protein transcriptional activity
are intimately linked to receptor activation, intracellular calcium levels, and activation of signaling pathways, such as
mitogen-activated protein kinases (66).
Although these relationships have not been worked out in
motoneurons, we have evidence that they may be similar to
those seen in hippocampus. Expression of BDNF, trkB, synapsin I, growth-associated protein-43, and cyclic AMP-responsive element binding protein are all increased in lumbar spinal
cord with voluntary exercise and decreased with muscle paralysis (40). Following spinal isolation (transection of the cord
above and below the motoneuron cell bodies, and section of
peripheral afferents to these motoneurons), expression of
BDNF and synapsin I, which is regulated by BDNF, is reduced
in the lumbar cord, but increased in the cervical cord, the latter
response presumably a forelimb overload effect (39). Evidence
of neurotrophin-related changes in motoneurons that are similar to those in hippocampus has led to the idea that motoneurons may be “learning” physical activity during the training
process (32).
MOTOR UNIT RECRUITMENT BEHAVIOR
Although we can obtain some insight into motoneuron
adaptations to training from human studies, this information is,
of course, limited by the complexities of voluntary movement
and of its integration in the spinal cord. However, some
observations are strongly suggestive of motoneuron adaptations; a few examples are cited below.
J Appl Physiol • VOL
In motor units of the first dorsal interosseus, recruitment
thresholds, average firing rates, initial firing rates, and firing
rate discharge variability are all significantly lower for the
dominant as opposed to the nondominant hand. All of these
changes would be consistent with an increased excitability
(lower, more clustered thresholds) and increased afterhyperpolarization (AHP) amplitudes and/or durations of motoneurons (lower initial firing rates, and less firing rate variability) with increased usage (1). This observation is consistent
with that of Cracraft and Petajan (19), who showed that 6
wk of low-intensity, moderate-duration endurance exercises
of the tibialis anterior resulted in less variable firing rates of
motor units.
Interestingly, ballistic-type training of the tibialis anterior
also resulted in a decrease in the recruitment thresholds of
motor units. Also, the authors contended that there was some
evidence that the increased presence of doublet discharges
following ballistic training might be due to changes in biophysical properties of the motoneuron, perhaps at the level of
delayed depolarization (65).
On the other hand, force-modulation or force-tracking training, which involves more skill than the training modes mentioned above, results in increased recruitment thresholds and
reduced firing frequencies of motor units at percentages of
maximal voluntary contraction (55). Such an adaptation would
allow more precise and accurate control of increments in
muscle force (12).
Although some reflex studies have suggested that motoneurons might have increased excitabilities following
training, this interpretation is tenuous, given the many
caveats in interpreting the H reflex (70). Although reflex
responses evoked during voluntary contractions are potentiated following strength training, the corresponding H reflexes
and F responses at rest are not, suggesting that changes in
intrinsic motoneuronal excitability are not involved in this
response (59).
ELECTROPHYSIOLOGY
Measurements of the biophysical properties of motoneurons
have been a fairly recent development, and some consistent
adaptations have been noted with increased activity (9, 10).
Evidence from recruitment studies referred to above might lead
us to expect changes with endurance training in measurements
of basic excitability, such as rheobase and input resistance, and
in properties such as the duration of the AHP, which is known
to influence firing rates. Intense endurance training for 16 wk
in rats resulted in hyperpolarized resting membrane potentials
(RMPs), hyperpolarized voltage thresholds (VT), faster action
potential rise times, and, in fast motoneurons, increased estimated capacitance in those motoneurons innervating the ankle
extensors/toe flexors (10). These measurements were made
24 – 48 h following the last training session and were, therefore, adaptations to the resting state of the motoneuron. When
exercise was of milder intensity, intermittent, and of longer
daily duration, in the form of continuous access to voluntary
exercise wheels, similar adaptations were found in RMP and
VT, with the added increase in the AHP amplitude, and these
adaptations were isolated to those motoneurons innervating
slow-twitch fibers.
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EFFECTS OF EXERCISE TRAINING ON ␣-MOTONEURONS
These observations allow us to make several statements.
First, motoneurons are sensitive to increased chronic activity
and respond with phenotypic changes. This adds to the evidence from biochemical and neuromuscular junction adaptations referred to above, that the motoneuron responds to a
change in its normal activity level. Second, it appears that some
properties are more sensitive to the intensity and/or the daily
duration of the overload (action potential rise time, AHP) than
others (RMP, VT). Third, it seems that motoneurons can adapt
in several functionally significant properties, without changes
in its signature properties that designate it as a fast or slow
motoneuron (such as AHP duration, rheobase, and input resistance) and that would be expected to change to explain recruitment behavior changes referred to in the previous section. In
the studies described above, properties that normally covary
significantly with the type of muscle fiber innervated (slow
fibers are innervated by motoneurons possessing longer AHPs,
lower rheobase currents, and higher input resistances) showed
no adaptations to training: the proportions of slow and fast
motoneurons were not influenced by training (not even any
tendencies in this direction were present).
These adaptations with increased activity are given more
credence by the finding that many of these changes occur in the
opposite direction when activity is reduced by hindlimb un-
1231
eling exercise to attempt to reproduce the biophysical changes
described above, by selectively altering ionic conductances. In
this way, we may have some insight into the ion channels that
are involved and perhaps that are modulated chronically with
increased activity.
MODELING MOTONEURONAL
ELECTROPHYSIOLOGICAL ADAPTATIONS
Since the electrophysiological changes with endurance training described above involve changes in ion conductances, we
proceeded to attempt to reproduce these changes in a mathematical model. Two motoneuron models (S and F type) were
built with GENESIS. The structure of the models was based on
the previous five-compartment models (22). The passive properties of the models were based on the data from rat lumbar
motoneurons (17, 52). The 10 active conductances included in
the models are fast sodium (gNa), persistent sodium (gNaP),
delayed rectifier (gKdr), calcium-dependent potassium (gKahp),
A-current (gKa), H current (gh), T-type calcium (gCaT), N-type
calcium (gCaN), L-type calcium (gCaL), and leak conductances,
which were mediated by potassium (gleak) and passive membrane current (gP). The distribution of the conductances was
the same as that described in the previous models (22). The
Hodgkin-Huxley equations for the ionic currents are written as
I Na ⫽ gNa 䡠 m3 䡠 h 䡠 共Vm ⫺ ENa兲; INaP ⫽ gNaP 䡠 m3 䡠 共Vm ⫺ ENa兲; IKdr ⫽ gKdr 䡠 n4 䡠 共Vm ⫺ EK兲;
I Kahp ⫽ gKahp 䡠 q 䡠 共Vm ⫺ EK兲; IKa ⫽ gKa 䡠 mA4 䡠 hA 䡠 共Vm ⫺ EK兲; Ih ⫽ gh 䡠 mh 䡠 共Vm ⫺ Eh兲;
I CaT ⫽ gCaT 䡠 m T3 䡠 hT 䡠 共Vm ⫺ ECa兲; ICaN ⫽ gCaN 䡠 mN2 䡠 hN 䡠 共Vm ⫺ ECa兲; ICaL ⫽ gCaL 䡠 mL 䡠 共Vm ⫺ ECa兲;
I leak ⫽ gleak 䡠 共Vm ⫺ EK兲; IP ⫽ gP 䡠 共Vm ⫺ Erest兲
weighting (17) and spinal cord transection (11). In the latter
model, changes in the depolarizing direction of RMP and VT,
as well as a shift in the frequency/current relationship to one of
reduced excitability, were prevented by daily passive exercise
of the paralyzed hindlimbs.
Interestingly, Cleary et al. (16) reported that motoneurons of
Aplysia involved in long-term behavioral training of the siphon
withdrawal reflex adapted with a hyperpolarization of the RMP
(of ⬃4 mV) and of the VT (of ⬃2 mV). Similarly, VT changes
measured from motoneurons in situ have been proposed as
possible mechanisms for the effects of operant conditioning on
H-reflex amplitudes in primates (14). For this reason, the
adaptive electrophysiological changes of motoneurons in
response to increased activity may arguably be considered,
to some extent, learning (32). Carroll et al. (15), using
transcranial magnetic and electrical stimulations to determine the effects of strength training in neural pathways,
concluded that changes in intrinsic properties of motoneurons,
similar to those summarized above, were consistent with their
results.
In summary, changes to motoneurons with exercise training
appear to include functional changes at the neuromuscular
synapse, alterations in protein synthesis, gene expression, and
axon transport, and some biophysical properties, which will
influence the manner in which these cells behave during
voluntary recruitment. In the next section, we present a modJ Appl Physiol • VOL
where INa is the current for fast Na⫹ channels; INaP, persistent
sodium; IKdr, delayed rectifier K⫹; IKahp, Ca2⫹-dependent K⫹;
IKa, A current; Ih, H current; ICaT, T-type Ca2⫹; ICaN, N-type
Ca2⫹; ICaL, L-type Ca2⫹; Ileak, leak current mediated by potassium; and IP, leak current mediated by passive membrane.
ENa, EK, ECa, and Eh are equilibrium potentials for Na⫹, K⫹,
Ca2⫹, and H currents and equal to 55, ⫺70, 80, and ⫺55 mV,
respectively. Erest is RMP and set to ⫺60 mV. Vm is membrane
voltage. Letters m, h, n, and q (with or without subscripts) are
membrane state variables that are defined by the HodgkinHuxley type equation:
dX
⫽ ␣共1 ⫺ X兲 ⫺ ␤X
dt
where steady-state value X⬁ ⫽ ␣/(␣ ⫹ ␤) and time constant
␶ ⫽ 1/(␣ ⫹ ␤).
The intracellular calcium concentration ([Ca2⫹]in) in the
soma and dendrite compartments satisfy the following equation
(64).
关Ca2⫹兴in
d关Ca2⫹兴in
⫽ BICaN ⫺
dt
␶Ca
where B is a scaling constant in arbitrary units and set to ⫺50
in the soma compartment and ⫺40 in the dendrite compart-
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EFFECTS OF EXERCISE TRAINING ON ␣-MOTONEURONS
1232
Table 1. The structure of the S- and F-type models
Compartment
Axon
IS
Soma
P dendrite
D dendrite
Diameter,
␮m
Length, ␮m
6
4
8
20
15
400
50
200
300†, 500*
400†, 600*
RM, ⍀cm2
5,400†,
5,400†,
5,400†,
5,400†,
5,400†,
4,500*
4,500*
4,500*
4,500*
4,500*
RA, ⍀cm
CM, ␮F/cm2
20
20
20
40
40
1.0
1.0
1.0
1.0
1.0
IS, initial segment; P, proximal; D, distal; RM, specific membrane
resistance; RA, specific axial resistance; CM, specific membrane capacitance. *Parameters for F-type model only. †Parameters for S-type model
only.
ment. ␶Ca is a time constant, the rate of decay of [Ca2⫹]in. It is
set to 20 ms for both soma and dendrite compartments. ICaN is
the N-type Ca2⫹ current.
The passive and active parameters of the models are shown
in Tables 1 and 2, respectively, and the membrane properties
ofthe real motoneurons and models are presented in Table 3.
Rate constants in the Hodgkin-Huxley equations are in the
APPENDIX. Note in Table 3 that the properties of rat motoneurons were fairly well depicted using this model.
The target values obtained from the experiments were set for
the modeling with some restrictions. The simulations were
performed on the principle that the least number of conductances was altered to achieve the most target values with no or
the least breakage of the restrictions. In this study, the VT,
RMP, and the maximum rising rate of action potentials were
set as the target values, whereas the rheobase, input resistance,
and frequency/current relationship were regarded as the restrictions. The AHP was set as both.
Table 4 summarizes our attempts to produce endurancetrained motoneurons using this modeling procedure. The simulation conditions in the far left column in Table 4 are changes
made in the model for control rat motoneurons, to simulate
training-induced adaptations in motoneuron properties. The
conditions are as follows:
1) Sodium conductance in soma and initial segment was
increased by 50%, with all other conductances remaining
unchanged.
2) Delayed-rectifier potassium conductance in soma and
initial segment was decreased by 50%.
3) Combination of conditions 1 and 2.
4) This is condition 1 with the addition of a 100% increase
in soma and dendrite leak conductance.
5) Increased sodium conductance as in condition 1, with the
addition of a 20% decrease in delayed rectifier potassium
conductance.
6) Condition 4, with the addition of a 50% increase in the
soma and dendrite potassium conductance associated with the
AHP.
Most of the changes involved changes in conductances of
the fast sodium and delayed-rectifier potassium conductances
in the soma and initial segment, as these conductances are
concentrated here. We can make a number of general observations from the data in Table 4. First, increased sodium
conductances are most likely involved, as the only condition
with no sodium conductance involvement failed to produce the
increased maximum rate of rise of the action potential seen
with endurance training. Second, an increase in leak conductance may occur with endurance training, as this increase, in
combination with an increased sodium conductance, resulted in
a hyperpolarized RMP (condition 4). Third, an increased delayed-rectifier potassium conductance is probably not involved, as this resulted in a dramatic increase in AHP halfdecay time, which did not occur with endurance training
(condition 5). In general, the conditions that seem to best
describe endurance training-induced adaptations in motoneurons are conditions 1, 3, 4, and 6, all of which involve at least
an increase in sodium conductance. Preliminary results suggest
that gene expression of the ␣-subunit of the fast sodium
conductance channel NaV1.6 is significantly upregulated as
soon as 5 days following initiation of a daily treadmill training
program.
ACUTE CHANGES IN MOTONEURON PROPERTIES
DURING EXERCISE
The electrical properties of spinal motoneurons are strongly
influenced by synaptic inputs with neuromodulatory actions via
G protein-coupled receptors. It is likely that levels of at lease
some of these neuromodulators are different during exercise
than during the resting state. The best studied neuromodulatory
input is the monoaminergic system, which originates in the
brain stem and includes axons releasing either serotonin (5HT) or norepinephrine (NE) (13). These two systems arise
from different brain stem areas (the caudal raphe nucleus for
5-HT and the locus coerulus for NE), but both project
throughout the length of the spinal cord, with branches
reaching both dorsal and ventral areas. In the ventral horn,
both 5-HT and NE have similar actions on motoneurons,
Table 2. Distribution and density of conductances
Axon
IS
Soma
P dendrite
D dendrite
gNa
gNaP
gKdr
gKahp
gKa
gKh
gCaT
gCaN
gCaL
gleak‡
1,200†, 1,000*
2,500†, 2,000*
2,000†, 1,800*
/
/
/
100
20
/
/
380
900
320
/
/
/
/
190
40
/
/
/
55
/
/
/
/
40
/
/
/
/
40
/
/
/
/
140
10
/
/
/
20
3
/
/
/
1†, 2*
4†, 6*
/
Values are in mS/cm2. gNa, maximum conductance for fast Na⫹ channels; gNaP, persistent sodium; gKdr, delayed rectifier K⫹; gKahp, Ca2⫹-dependent K⫹; gKa,
A current; gh, h current; gCaT, T-type Ca2⫹; gCaN, N-type Ca2⫹; gCaL, L-type Ca2⫹; gleak, leak current mediated by potassium; gP, leak current mediated by passive
membrane. *Parameters for F-type model only. †Parameters for S-type model only. /, No conductance is included. ‡The leak conductance mediated by passive
membrane resistance (gP) is not shown in this table. It is calculated by gP ⫽ (A/RM)*S, where A is the area of the compartments, RM is the specific membrane
resistance, and S (⫽ 1⬃3) is a scaling factor for adjustment of the passive membrane properties.
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EFFECTS OF EXERCISE TRAINING ON ␣-MOTONEURONS
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Table 3. Membrane properties of the real motoneurons (mean values) and the models
Motoneurons (S)
Motoneurons (F)
Model (S)
Model (F)
Irhe, nA
Rin, M⍀
AHP 1/2 Decay, ms
AHP Amplitude, mV
Vth, mV
RMP, mV
␶m, ms
F/I Slope, Hz/nA
Soma Area, ␮m2
6
8
5.3
7.8
2.7
1.7
2.3
1.5
29
14
36.2
26.7
4.3
2.4
4.7
3.1
⫺42
⫺43
⫺39.8
⫺41.7
⫺63
⫺61
⫺61.4
⫺61.2
5.4
4.5
5.5
4.5
4.5
4.6
4.4
4.7
4,392.1
5,208.8
5,024
5,024
S, S type; F, F type; Irhe, rheobase current; Rin, cell input resistance; AHP 1/2 decay, afterhyperpolarization half-decay time; AHP amplitude, afterhyperpolarization amplitude; Vth, voltage threshold of the action potential; RMP, resting membrane potential; ␶m, membrane time constant; F/I slope, slope of the
frequency/current relationship. Notes (measurement of the model parameters): Irhe was measured by a step depolarization current of 0.5 s, and Rin by a
hyperpolarization current of 0.5 s and ⫺1 nA. AHP was measured from a single spike evoked by a short pulse of 2 ms and 10 nA. Vth was averaged from a
spike train evoked by the minimum current (0.5 s) for the repetitive firing.
markedly enhancing their excitability by several mechanisms, including facilitation of persistent inward currents,
depolarization of the RMP, hyperpolarization of action
potential threshold, and reduction in the amplitude of the
AHP (2, 37, 41, 44, 56, 57). The monoaminergic systems are
highly state dependent, with the serotonergic system being
especially active during tonic motor output (47) and the
noradrenergic system varying with state of arousal (8). Thus,
during exercise, motoneuron excitability should markedly increase (46, 47).
It is interesting to note that neuromodulatory effects of
monoamines and adaptations to exercise have opposite actions on motoneuron resting potential (monoamines depolarize, exercise hyperpolarizes). The increase in AHP amplitude with longer duration exercise in S motoneurons is
also opposite of the monoaminergic action. Parallel effects
are seen on threshold voltage (hyperpolarized in both cases).
Thus, in part, the exercise adaptations may be a response to
the increased excitability mediated by the monoaminergic
input.
From a functional viewpoint, the key issue is the difference between the RMP and the action potential VT of the
motoneuron. This difference can be assessed by measuring
the injected current required to initiate an action potential,
i.e., the cell rheobase. Because the hyperpolarization of
action potential VT and RMP is about equal, rheobase stays
about the same (9, 10). Yet neuron excitability is compli-
cated: the exercise-induced hyperpolarizing shift in action
potential VT coupled with the increased AHP would tend to
hyperpolarize the average membrane potential during repetitive firing. This hyperpolarization may reduce the activation of persistent inward currents and thus generate a lower
level of excitability for prolonged inputs. It is thus possible
that exercise does adapt motoneurons to a lower state of
excitability, but clearly more experiments need to address
the interaction between exercise and persistent inward currents.
SUMMARY AND CONCLUSIONS
␣-Motoneurons adapt to training by changing several of
their properties (Fig. 1). While many of the adaptations seem
destined to have functional consequences during endurance
exercise (increased capacities for axon transport and for
neurotransmitter release), many others do not seem to have
obvious functional implications for enhanced neuromuscular performance (hyperpolarization of RMP and action potential threshold, and increased amplitude of AHPs). Future
studies will be required to study motoneurons under conditions that are closer to the in vivo situation during endurance
exercise, or with model motoneurons, to determine how motoneurons behave during endurance exercise, with and without
altered properties.
Table 4. Changes in membrane properties induced by alteration of conductances to make the cells “endurance trained”
Simulation
Conditions
Irhe, nA
Rin, M⍀
1
2
3
4
5
6
⫺2.4
⫺1.4
⫺3.1
0
⫺2
0
0*
0
0
⫺0.2
0
⫺0.2
1
3.1
3.7
0.9
3.4
6.4
0
0
0
⫺0.8
0
0
1
2
3
4
5
6
⫺1.2
⫺1.2
⫺1.8
0
⫺0.9
0.6
0
0
0
⫺0.4
0
⫺0.5
2
0.8
1.5
⫺2.6
10.7
4.9
0
0
⫺1
⫺0.8
0
0
AHP 1/2 Decay, ms
AHP Amplitude, mV
Vth, mV
RMP, mV
Max dV/dt, mV/ms
F/I Curve
⫺6.4
⫺2.5
⫺7.8
⫺5.4
⫺4.9
⫺4.7
0
0
0
⫺3.0
0
⫺3.1
13.2
0
17.2
14.7
12.3
15.0
left shift
left shift
left shift
no shift
left shift
no shift (slope increased)
⫺4.1
⫺2.9
⫺4.4
⫺3.7
⫺3.5
⫺3.5
0
0
0
⫺2.0
0
⫺1.9
15
0
16.7
13.2
16.1
13.3
left shift
left shift
left shift
no shift (slope decreased)
no shift (slope decreased)
no shift (slope increased)
F type
S type
Max dV/dt, maximum rate of rise of the action potential.
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EFFECTS OF EXERCISE TRAINING ON ␣-MOTONEURONS
1234
APPENDIX
Table 1A. Rate constants in Hodgkin-Huxley equations (resting membrane equilibrium potential ⫽ 60 mV)
Conductance
gNa
Compartment
Forward (␣)
Backward (␤)
⫺0.4(55 ⫹ V)
55 ⫹ V
exp
⫺1
⫺5
35 ⫹ V
␣h ⫽ 0.28 exp
⫺20
冉
S type: ␣m ⫽
Initial segment
冉
冊
冊
⫺0.4(60 ⫹ V)
60 ⫹ V
exp
⫹1
⫺5
40 ⫹ V
␣h ⫽ 0.28 exp
⫺20
冉
F type: ␣m ⫽
冉
⫺0.4(42.5 ⫹ V)
42.5 ⫹ V
exp
⫺1
⫺5
35 ⫹ V
␣h ⫽ 0.28 exp
⫺20
␣m ⫽
Axon and soma
gNaP
Initial segment and soma
gKdr
Initial segment
Axon and soma
gKa
Soma
gh
Soma
gCaT
Soma
gCaN
冊
冊
Soma and dendrite
冉
冊
冉
冊
⫺0.4(52.5 ⫹ V)
52.5 ⫹ V
exp
⫺1
⫺5
⫺0.02(50 ⫹ V)
␣n ⫽
50 ⫹ V
exp
⫺1
⫺10
⫺0.02(40 ⫹ V)
␣n ⫽
40 ⫹ V
⫺1
exp
⫺10
0.032(V ⫹ 54)
␣mA ⫽
V ⫹ 54
1 ⫺ exp
⫺6
0.05
␣hA ⫽
V ⫹ 76
1 ⫹ exp
10
0.06
␣mh ⫽
V ⫹ 75
1 ⫹ exp
5.3
0.02(V ⫹ 38)
␣mT ⫽
V ⫹ 38
1 ⫺ exp
⫺4.5
⫺0.0001(V ⫹ 43)
␣hT ⫽
V ⫹ 43
1 ⫺ exp
7.8
0.2
␣mN ⫽
V ⫹ 20
1 ⫹ exp
6.13
0.05
␣hN ⫽
V⫹35
1 ⫹ exp
⫺55.2
0.025
␣mL ⫽
V ⫹ 30
1 ⫹ exp
⫺7
␣q ⫽ 10⫺3 [Ca2⫹]A2
␣m ⫽
冉
冊
冉
冊
冉
冊
冉
冊
冉
冊
冉
冊
冉
冊
冉
冊
冉
冊
冉 冊
gCaL
Soma and dendrite
gKahp
Soma and dendrite
冉
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0.4(V ⫹ 30)
V ⫹ 30
exp
⫺1
5
4
␤h ⫽
35 ⫹ V
exp
⫹1
⫺10
0.4(V ⫹ 35)
␤m ⫽
V ⫹ 35
exp
⫺1
5
4
␤h ⫽
40 ⫹ V
exp
⫹1
⫺10
0.4(V ⫹ 15)
␤m ⫽
V ⫹ 15
exp
⫺1
5
4
␤h ⫽
20 ⫹ V
⫹1
exp
⫺10
0.4(V ⫹ 25)
␤m ⫽
V⫹ 25
exp
⫺1
5
60 ⫹ V
␤n ⫽ 0.25 exp
⫺80
␤m ⫽
冉
冊
冉
冊
冉
冊
冉
冊
冉
冊
冉
冊
冉 冊
冉 冊
冉
␤n ⫽ 0.25 exp
冊
50 ⫹ V
⫺80
0.203
V⫹30
exp
24
0.05
␤h A ⫽
V ⫹ 76
1 ⫹ exp
⫺10
0.06
␤m h ⫽
V ⫹ 75
1 ⫹ exp
⫺5.3
⫺0.05(V ⫹ 41)
␤m T ⫽
V ⫹41
1 ⫺ exp
4.5
0.03
␤h T ⫽
V⫹ 41
1 ⫹ exp
⫺4.8
0.2
␤m N ⫽
V ⫹ 20
1 ⫹ exp
⫺55.2
0.05
␤h N ⫽
V ⫹ 35
1 ⫹ exp
6.13
0.025
␤m L ⫽
V ⫹ 30
1 ⫹ exp
7
␤q ⫽ 0.4
␤m A ⫽
冉 冊
冉
冊
冉
冊
冉 冊
冉 冊
冉
冊
冉
冊
冉
冊
Invited Review
EFFECTS OF EXERCISE TRAINING ON ␣-MOTONEURONS
ACKNOWLEDGMENTS
The authors acknowledge our graduate students, who have helped shape
these thoughts over many years in the laboratory. Thanks also to Maria
Setterbom for the figure.
GRANTS
The authors acknowledge funding support from Canadian Institutes of
Health Research, Canadian Space Agency, National Sciences and Engineering
Research Council, The Canada Research Chairs Program, and the National
Institutes of Health.
REFERENCES
1. Adam A, De Luca CJ, and Erim Z. Hand dominance and motor unit
firing behavior. J Neurophysiol 80: 1373–1382, 1998.
2. Alaburda A, Perrier JF, and Hounsgaard J. Mechanisms causing
plateau potentials in spinal motoneurones. Adv Exp Med Biol 508: 219 –
226, 2002.
3. Alessandri-Haber N, Alcaraz G, Deleuze C, Jullien F, Manrique C,
Couraud F, Crest M, and Giraud P. Molecular determinants of emerging excitability in rat embryonic motoneurons. J Physiol 541: 25–39,
2002.
4. Alvarez FJ, Dewey DE, Carr PA, Cope TC, and Fyffe REW. Downregulation of metabotropic glutamate receptor 1a in motoneurons after
axotomy. Neuroreport 8: 1711–1716, 1997.
5. Andersson Y and Edstrom JE. Motor hyperactivity resulting in diameter
decrease of peripheral nerves. Acta Physiol Scand 39: 240 –245, 1957.
6. Andonian MH and Fahim MA. Endurance exercise alters the morphology of fast- and slow-twitch rat neuromuscular junctions. Int J Sports Med
9: 218 –223, 1988.
7. Argaw A, Desaulniers P, and Gardiner PF. Enhanced neuromuscular
transmission efficacy in overloaded rat plantaris muscle. Muscle Nerve 29:
97–103, 2004.
8. Aston-Jones G, Rajkowski J, and Cohen J. Locus coeruleus and
regulation of behavioral flexibility and attention. Prog Brain Res 126:
165–182, 2000.
9. Beaumont E and Gardiner P. Effects of daily spontaneous running on
the electrophysiological properties of hindlimb motoneurones in rats.
J Physiol 540: 129 –138, 2002.
10. Beaumont E and Gardiner PF. Endurance training alters the biophysical
properties of hindlimb motoneurons in rats. Muscle Nerve 27: 228 –236,
2003.
11. Beaumont E, Houlé JD, Peterson CA, and Gardiner PF. Passive
exercise and fetal spinal cord transplant both help to restore motoneuronal
properties after spinal cord transection in rats. Muscle Nerve 29: 234 –242,
2004.
12. Bernardi M, Solomonow M, Nguyen G, Smith A, and Baratta R.
Motor unit recruitment strategy changes with skill acquisition. Eur J Appl
Physiol 74: 52–59, 1996.
13. Bjorklund A and Skagerberg G. Descending monoaminergic projections
in the spinal cord. In: Brain Stem Control of Spinal Mechanisms, edited by
Sjolund BA. Amsterdam: Elsevier Biomedical, 1982, p. 55– 88.
14. Carp JS and Wolpaw JR. Motoneuron properties after operantly conditioned increase in primate H-reflex. J Neurophysiol 73: 1365–1373, 1995.
15. Carroll TJ, Riek S, and Carson RG. The sites of neural adaptation
induced by resistance training in humans. J Physiol 544: 641– 652, 2002.
16. Cleary LJ, Lee WL, and Byrne JH. Cellular correlates of long-term
sensitization in Aplysia. J Neurosci 18: 5988 –5998, 1998.
17. Cormery B, Beaumont E, Csukly KJ, and Gardiner PF. Hindlimb
unweighting for two weeks alters physiological properties of rat hindlimb
motoneurones. J Physiol 568: 841– 850, 2005.
18. Cormery B, Marini JF, and Gardiner PF. Changes in electrophysiological properties of tibial motoneurones in the rat following 4 weeks of
tetrodotoxin-induced paralysis. Neurosci Lett 287: 21–24, 2000.
19. Cracraft JD and Petajan JH. Effect of muscle training on the pattern of
firing of single motor units. Am J Phys Med Rehabil 56: 183–194, 1977.
20. Czeh G, Gallego R, Kudo N, and Kuno M. Evidence for the maintenance of motoneurone properties by muscle activity. J Physiol 281:
239 –252, 1978.
21. Dahlstrom A, Heiwall PO, Booj S, and Dahllof AG. The influence of
supraspinal impulse activity on the intra-axonal transport of acetylcholine,
choline acetyltransferase and acetylcholinesterase in rat motor neurons.
Acta Physiol Scand 103: 308 –319, 1978.
J Appl Physiol • VOL
1235
22. Dai Y, Jones KE, Fedirchuk B, McCrea DA, and Jordan LM. A
modelling study of locomotion-induced hyperpolarization of voltage
threshold in cat lumbar motoneurones. J Physiol 544: 521–536, 2002.
23. Desaulniers P, Lavoie PA, and Gardiner PF. Endurance training increases acetylcholine receptor quantity at neuromuscular junctions of adult
rat skeletal muscle. Neuroreport 9: 3549 –3552, 1998.
24. Desaulniers P, Lavoie PA, and Gardiner PF. Habitual exercise enhances neuromuscular transmission efficacy of rat soleus muscle in situ.
J Appl Physiol 90: 1041–1048, 2001.
25. Deschenes MR, Maresh CM, Crivello JF, Armstrong LE, Kraemer
WJ, and Covault J. The effects of exercise training of different intensities
on neuromuscular junction morphology. J Neurocytol 22: 603– 615, 1993.
26. Donselaar Y, Kernell D, and Eerbeek O. Soma size and oxidative
enzyme activity in normal and chronically stimulated motoneurones of the
cat’s spinal cord. Brain Res 385: 22–29, 1986.
27. Dorlöchter M, Irintchev A, Brinkers M, and Wernig A. Effects of
enhanced activity on synaptic transmission in mouse extensor digitorum
longus muscle. J Physiol 436: 283–292, 1991.
28. Eadie BD, Redila VA, and Christie BR. Voluntary exercise alters the
cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density. J Comp Neurol 486:
39 – 47, 2005.
29. Edds MV Jr. Hypertrophy of nerve fibers to functionally overloaded
muscles. J Comp Neurol 93: 259 –275, 1950.
30. Edstrom JE. Effects of increased motor activity on the dimensions and
the staining properties of the neuron soma. J Comp Neurol 107: 295–304,
1957.
31. Gardiner P, Michel R, and Iadeluca G. Previous exercise training
influences functional sprouting of rat hindlimb motoneurons in response to
partial denervation. Neurosci Lett 45: 123–127, 1984.
32. Gardiner PF, Beaumont E, and Cormery B. Motoneurones “learn” and
“forget” physical activity. Can J Appl Physiol 30: 352–370, 2005.
33. Gardiner PF and Faltus RE. Contractile responses of rat plantaris
muscles following partial denervation, and the influence of daily exercise.
Pflügers Arch 406: 51–56, 1986.
34. Gazula VR, Roberts M, Luzzio C, Jawad AF, and Kalb RG. Effects of
limb exercise after spinal cord injury on motor neuron dendrite structure.
J Comp Neurol 476: 130 –145, 2004.
35. Gerchman LB, Edgerton VR, and Carrow RE. Effects of physical
training on the histochemistry and morphology of ventral motor neurons.
Exp Neurol 49: 790 – 801, 1975.
36. Gharakhanlou R, Chadan S, and Gardiner P. Increased activity in the
form of endurance training increases calcitonin gene-related peptide content in lumbar motoneuron cell bodies and in sciatic nerve in the rat.
Neuroscience 89: 1229 –1239, 1999.
37. Gilmore J and Fedirchuk B. The excitability of lumbar motoneurones in
the neonatal rat is increased by a hyperpolarization of their voltage
threshold for activation by descending serotonergic fibres. J Physiol 558:
213–224, 2004.
38. Gisiger V, Bélisle M, and Gardiner PF. Acetylcholinesterase adaptation
to voluntary wheel running is proportional to the volume of activity in fast,
but not slow, rat hindlimb muscles. Eur J Neurosci 6: 673– 680, 1994.
39. Gómez-Pinilla F, Ying Z, Roy RR, Hodgson J, and Edgerton VR.
Afferent input modulates neurotrophins and synaptic plasticity in the
spinal cord. J Neurophysiol 92: 3423–3432, 2004.
40. Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, and Edgerton VR.
Voluntary exercise induces a BDNF-mediated mechanism that promotes
neuroplasticity. J Neurophysiol 88: 2187–2195, 2002.
41. Heckman CJ, Gorassini M, and Bennett DLH. Persistent inward currents in motoneuron dendrites: implications for motor control. Muscle
Nerve 31: 135–156, 2005.
42. Henderson CE, Phillips HS, Pollock RA, Davies AM, Lemeulle C,
Armanini M, Simpson LC, Moffet B, Vandlen RA, Koliatsos VE, and
Rosenthal A. GDNF: a potent survival factor for motoneurons present in
peripheral nerve and muscle. Science 266: 1062–1064, 1994.
43. Hochman S and McCrea D. Effects of chronic spinalization on ankle
extensor motoneurons. II. Motoneuron electrical properties. J Neurophysiol 71: 1468 –1479, 1994.
44. Hultborn H. Plateau potentials and their role in regulating motoneuronal
firing. Prog Brain Res 123: 39 – 48, 1999.
45. Ishihara A, Kawano F, Ishioka N, Oishi H, Higashibata A, Shimazu T,
and Ohira Y. Effects of running exercise during recovery from hindlimb
101 • OCTOBER 2006 •
www.jap.org
Invited Review
1236
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
EFFECTS OF EXERCISE TRAINING ON ␣-MOTONEURONS
unloading on soleus muscle fibers and their spinal motoneurons in rats.
Neurosci Res 48: 119 –127, 2004.
Jacobs BL and Fornal CA. Serotonin and motor activity. Curr Opin
Neurobiol 7: 820 – 825, 1997.
Jacobs BL, Martı́n-Cora FJ, and Fornal CA. Activity of medullary
serotonergic neurons in freely moving animals. Brain Res Rev 40: 45–52,
2002.
Jasmin B, Lavoie PA, and Gardiner PF. Fast axonal transport of
acetylcholinesterase in rat sciatic motoneurons is enhanced following
prolonged daily running, but not following swimming. Neurosci Lett 78:
156 –160, 1987.
Jasmin B, Lavoie P, and Gardiner P. Fast axonal transport of labeled
proteins in motoneurons of exercise-trained rats. Am J Physiol Cell
Physiol 255: C731–C736, 1988.
Kang CM, Lavoie PA, and Gardiner PF. Chronic exercise increases
SNAP-25 abundance in fast-transported proteins of rat motoneurones.
Neuroreport 6: 549 –553, 1995.
Lnenicka GA and Atwood HL. Impulse activity of a crayfish motoneuron regulates its neuromuscular synaptic properties. J Neurophysiol 61:
91–96, 1986.
Miles GB, Dai Y, and Brownstone RM. Mechanisms underlying the
early phase of spike frequency adaptation in mouse spinal motoneurones.
J Physiol 566: 519 –532, 2005.
Nakano H, Masuda K, Sasaki SY, and Katsuta S. Oxidative enzyme
activity and soma size in motoneurons innervating the rat slow-twitch and
fast-twitch muscles after chronic activity. Brain Res Bull 43: 149 –154,
1997.
Neeper SA, Gómez-Pinilla F, Choi J, and Cotman C. Exercise and brain
neurotrophins. Nature 373: 109, 1995.
Patten C and Kamen G. Adaptations in motor unit discharge activity
with force control training in young and older human adults. Eur J Appl
Physiol 83: 128 –143, 2000.
Powers RK and Binder MD. Input-output functions of mammalian
motoneurons. Rev Physiol Biochem Pharmacol 143: 137–263, 2001.
Rekling JC, Funk GD, Bayliss DA, Dong XW, and Feldman JL.
Synaptic control of motoneuronal excitability. Physiol Rev 80: 767– 852,
2000.
Roy RR, Gilliam TB, Taylor JF, and Heusner WW. Activity-induced
morphologic changes in rat soleus nerve. Exp Neurol 80: 622– 632, 1983.
J Appl Physiol • VOL
59. Sale DG, MacDougall JD, Upton ARM, and McComas AJ. Effect of
strength training upon motoneuron excitability in man. Med Sci Sports
Exerc 15: 57– 62, 1983.
60. Samorajski T and Rolsten C. Nerve fiber hypertrophy in posterior tibial
nerves of mice in response to voluntary running activity during aging.
J Comp Neurol 159: 553–558, 1975.
61. Seburn K, Coicou C, and Gardiner P. Effects of altered muscle
activation on oxidative enzyme activity in rat ␣-motoneurons. J Appl
Physiol 77: 2269 –2274, 1994.
62. Soucy M, Seburn K, and Gardiner P. Is increased voluntary motor
activity beneficial or detrimental during the period of motor nerve regeneration/reinnervation? Can J Appl Physiol 21: 218 –224, 1996.
63. Suzuki H, Tsuzimoto H, Ishiko T, Kasuga N, Taguchi S, and Ishihara
A. Effect of endurance training on the oxidative enzyme activity of soleus
motoneurons in rats. Acta Physiol Scand 143: 127–128, 1991.
64. Traub RD, Wong RK, Miles R, and Michelson H. A model of a CA3
hippocampal pyramidal neurone incorporating voltage-clamp data on
intrinsic conductances. J Neurophysiol 66: 635– 650, 1991.
65. Van Cutsem M, Duchateau J, and Hainaut K. Changes in single motor
unit behaviour contribute to the increase in contraction speed after dynamic training in humans. J Physiol 513: 295–305, 1998.
66. Vaynman S, Ying Z, and Gomez-Pinilla F. Interplay between brainderived neurotrophic factor and signal transduction modulators in the
regulation of the effects of exercise on synaptic-plasticity. Neuroscience
122: 647– 657, 2003.
67. Vaynman S, Ying Z, and Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur
J Neurosci 20: 2580 –2590, 2004.
68. Waerhaug O, Dahl H, and Kardel K. Different effects of physical
training on the morphology of motor nerve terminals in the rat extensor
digitorum longus and soleus muscles. Anat Embryol (Berl) 186: 125–128,
1992.
69. Wu WT, Li LX, Yick LW, Chai H, Xie YY, Yang Y, Prevette DM, and
Oppenheim RW. GDNF and BDNF alter the expression of neuronal
NOS, c-Jun, and p75 and prevent motoneuron death following spinal root
avulsion in adult rats. J Neurotrauma 20: 603– 612, 2003.
70. Zehr EP. Considerations for use of the Hoffmann reflex in exercise
studies. Eur J Appl Physiol 86: 455– 468, 2002.
71. Zurn AD, Winkel L, Menoud A, Djabali K, and Aebischer P. Combined effects of GDNF, BDNF, and CNTF on motoneuron differentiation
in vitro. J Neurosci Res 44: 133–141, 1996.
101 • OCTOBER 2006 •
www.jap.org