J Physiol 589.
4 (2011) pp 775776
PERSPECTIVES
Muscle memory
Qiang Liu and Erik Jorgensen
HHMI/Department of Biology, University
of Utah, 257 S 1400 E, Salt Lake City,
UT 84112-0840, USA
Email: jorgensen@biology.utah.edu
In the movie Burn after reading, George
Clooney sings the praises of muscle
memory the concept that muscles have
excitable circuitry capable of directing
complex behaviour on their own. Sure
enough, when the moment comes his
muscles remember to rapidly draw a
The Journal of Physiology
gun and shoot a man who inadvertently
surprises him. Normally, Coen Brothers
movies are not a reliable source for
information about neuroscience, but in
this case they touched upon an inter-
esting controversy. Can muscles really drive
behaviour independent of the nervous
system? Alternating muscle contractions in
locomotion are thought to be generated
by a central pattern generator a neuro-
nal circuit (Grillner, 2006). But muscles can
fire action potentials and produce rhythmic
contractions without neuronal input no
one doubts that the heart keeps its own
counsel. Is it possible that body muscles
could direct locomotory behaviour on their
own? In a recent issue of The Journal of
Physiology, Zhao-Wen Wangs group (Liu
et al. 2011) suggests that it is possible.
Nematodes move by propagating a
rhythmic sinusoidal wave consisting of
alternating dorsal and ventral contractions
along their body. These rhythmic waves
propel them along surfaces or in liquid.
Early behavioural studies on the large
parasitic nematode Ascaris lumbricoides
demonstrated that the initiation and
propagation of contractile waves continue
after the head and the tail are excised
(Crofton, 1971). This result indicates that
the head and tail ganglia are not required
for coordinated locomotion worms do
not need a brain to move. Do they need a
nervous system at all? Weisblat and Russell
observed that Ascaris body muscles generate
spontaneous voltage spikes independent of
the nervous system (Weisblat & Russell,
1976). Moreover, Walrond and Stretton
demonstrated that voltage spikes in the
muscles propagate along the body via gap

C 2011 The Authors. Journal compilation 
C 2011 The Physiological Society
junctions between adjacent muscles cells
(Walrond & Stretton, 1985). These early
studies suggest that muscles themselves
are capable of generating and propagating
oscillatory contractions down the length of
the worm.
C. elegans is one hundred times
smaller than Ascaris but the number
of motoneurons is identical. Similarly,
C. elegans body-wall muscles are coupled
by gap junctions and genetic disruption
of these gap junctions results in an
extremely uncoordinated worm (Liu
et al. 2006). Mutants with severe defects in
neurotransmission or lacking acetylcholine
receptors are still capable of moving,
although very slowly (Richmond et al.
2001; Francis et al. 2005). Thus, there is
reason to believe that C. elegans muscles
may function in a similar fashion to
Ascaris.
On the other hand, evidence that the
motoneurons provide instructional input
into muscle contractions is overwhelming:
mutants lacking innervations from the
motoneurons, as opposed to defects
in neurotransmission, are essentially
paralysed. Moreover, the inputs from
the motoneurons and the response in
the muscles are thought to be graded
rather than coded by action potentials
for several reasons. First, synaptic output
from motoneurons is graded; the rate of
tonic miniature currents is proportional
to neuronal membrane potential (Liu
et al. 2009). Second, nematode muscles
simultaneously receive inputs from
excitatory and inhibitory motoneurons;
muscle contractions appear to be a
graded integration of these inputs. Third,
nematodes lack voltage-gated sodium
channels that would amplify synaptic
inputs into all-or-nothing depolarizations
in the muscle. These conclusions have been
experimentally supported: physiological
recordings demonstrate that body muscles
are non-spiking and non-oscillating cells
(Jospin et al. 2002). A modelling study
further indicated that the conductance
of gap junctions between muscles is too
small to play significant roles in rhythm
generation (Boyle & Cohen, 2008). These
authors concluded that C. elegans body
muscles function simply to execute the
orders imposed by the neurons. However,
would these conclusions change if it could
775
be shown that body muscles are capable of
spiking and oscillating?
The article by Liu et al. (2011) reports
that there are all-or-none action potentials
in C. elegans muscles. This study from
Zhao-Wen Wangs laboratory demonstrates
that these action potentials are calcium
dependent and occur in spontaneous trains.
By recording from mutant animals, Liu
and colleagues identified the ion channels
that contribute to these action potentials:
calcium influx through L-type and T-type
calcium channels, and calcium release from
internal stores via the ryanodine receptor
are responsible for the upstroke and peak
of the muscle action potential; shaker
and BK potassium channels shape the
repolarization.
Interestingly, Liu et al. found that body wall
muscles continue to fire action potentials
even when both acetylcholine and GABA
neuronal inputs were blocked. These results
suggest that C. elegans muscles may have
intrinsic oscillations independent of the
nervous system.
Do these spike trains cause muscle
contraction? The authors simultaneously
monitored intracellular calcium
fluctuations, muscle action potentials
and muscle contractions. They found that
in dissected preparations calcium transients
were correlated with clusters of action
potentials, and that in intact animals,
calcium transients were correlated with
muscle contractions. These observations
indicate a one-to-one correlation between
calcium spike trains and muscle contraction
in vivo. Furthermore, the authors noticed
that intact animals with greatly reduced
synaptic inputs still exhibit calcium trans-
ients in muscles. These data suggest how
animals without functional neuronal inputs
are still capable of moving. In the end this
study is consistent with the model that
muscles may be able to drive a contractile
wave on their own.
So is the issue settled? One caveat is
that the calcium transients detected from
the animals with severe synaptic defects
have reduced amplitudes and somewhat
irregular shape compared to those from
wild-type animals. It is not clear whether
these smaller calcium transients are caused
by all-or-none action potentials or sub-
threshold membrane potential fluctuations.
Thus, these results do not preclude the
DOI: 10.1113/jphysiol.2011.205088
776
possibility that motoneurons initiate the
muscle action potentials in vivo and
that the action potentials are propagated
spontaneously ex vivo. In other words,
muscle contractions could still require
neuronal inputs to initiate and shape the
pattern of muscle action potentials. But a
dissected muscle may become independent
of neuronal inputs due to the loss of
peptidergic signals, for example. Thus, it is
not clear yet whether C. elegans follows the
demands of the head or the heart. A full
exploration of these issues requires future
in-depth studies of the C. elegans motor
circuit.
Perspectives
References
Boyle JH & Cohen N (2008). Biosystems 94,
170181.
Crofton HD (1971). Form, function and
behavior. In Plant Parasitic Nematodes, eds
Zuckerman BM, Mai WF & Rhode RA, vol. III,
pp. 83116. Academic Press, Inc., New York.
Francis MM, Evans SP, Jensen M, Madsen DM,
Mancuso J, Norman KR & Maricq AV (2005).
Neuron 46, 581594.
Grillner S (2006). Neuron 52, 751766.
Jospin M, Jacquemond V, Mariol MC, Segalat L
& Allard B (2002). J Cell Biol 159, 337348.

C 2011 The Authors. Journal compilation 
J Physiol 589.4
Liu P, Ge Q, Chen B, Salkoff L, Kotlikoff MI &
Wang ZW (2011). J Physiol 589, 101117.
Liu Q, Chen B, Gaier E, Joshi J & Wang ZW
(2006). J Biol Chem 281, 78817889.
Liu Q, Hollopeter G & Jorgensen EM (2009).
Proc Natl Acad Sci U S A 106, 1082310828.
Richmond JE, Weimer RM & Jorgensen EM
(2001). Nature 412, 338341.
Walrond JP & Stretton AO (1985). J Neurosci 5,
1622.
Weisblat DA & Russell RL (1976). J Comp Physiol
A Neuroethol Sens Neural Behav Physiol 107,
293307.
C 2011 The Physiological Society