Learning and Memory in Invertebrates: C.
Elegans 413
Learning and Memory in Invertebrates: C. Elegans
T A Timbers and C H Rankin, The University of British
Columbia, Vancouver, BC, Canada
ã 2009 Elsevier Ltd. All rights reserved.
Introduction
In the 1960s Sydney Brenner and many colleagues
shared the view that most of the ‘interesting’ pro-
blems of molecular biology had been, or were close
to being, solved. It was their opinion that the nervous
system was the next frontier of science, as it appeared
to pose the most challenging questions. As a result,
the search began for an organism that would allow
for a global approach that focused on investigating
the nervous system by means of genetic dissection.
Brenner, after searching through many zoology texts,
and examining a number of animals, settled on our
organism of discussion, Caenorhabditis elegans. The
worm, as it is often affectionately called, fit his search
criteria for the ideal model organism: (1) it has a rapid
lifecycle allowing for growth of large populations in a
short period of time (C. elegans begins laying eggs at
3 days of age), (2) it has a simple reproductive cycle
and genome (hermaphrodites can reproduce clonally,
reducing the problem of differing genetic background
between individuals), and (3) it is small in size and
can be successfully frozen and thawed alive, making
for easy storage in the lab.
Since the beginning of its development as a model
organism a great wealth of knowledge has accumu-
lated, including a fully sequenced genome, a complete
wiring diagram of the nervous system, the develop-
mental lineage for every cell present in the adult
worm, and thousands of genetic mutants. The worm
is amendable to in vivo whole-organism molecular
analyses through the combination of microscopy
and genetic-based fluorescence imaging, allowing
for insight into protein localization and function.
Past research has shown that to a great extent the
cellular machinery and processes used by the worm
are homologous to those found in the other organ-
isms, including mammals. And of interest to the neuro-
scientist, C. elegans exhibits many basic types of
behaviors which can be analyzed at behavioral, neu-
ral circuit, and genetic levels.
Although the tiny worm has the smallest nervous
system of all multicellular learning and memory
model systems, with only 302 neurons at its disposal,
it shows a remarkable ability to learn and remember.
It has been shown capable of both associative and non-
associative learning and has recently been developed
as a model in which to study cellular mechanisms of
learning and memory. This article discusses the behav-
ioral paradigms used to study learning and memory in
C. elegans as well as the proposed cellular and molecu-
lar mechanisms. The different paradigms are divided
and discussed based upon their sensory modalities.
Mechanosensory Learning and Memory
The first type of learning described for C. elegans was
habituation to a mechanosensory stimulus. In this
learning paradigm the worm receives a mechanical
stimulus, a tap, applied to the side of the petri plate
within which it resides. The tap results in the worm
changing from a forward swimming motion to a
backward one for a brief period of time, after which
it swims forward again. This reversal response is
termed the ‘tap withdrawal’ response. This is indeed
habituation to the mechanical stimulus and not sen-
sory adaptation or fatigue, as the worm’s response to
tap can be dishabituated. After habituation training
the application of a more intense stimulus, such as an
electrical shock administered through the agar, causes
dishabituation such that worms will respond to the
subsequent presentation of the tap stimulus as if it
were novel.
The neural circuit that mediates this response has
been mapped and consists of mechanosensory neu-
rons, command interneurons, and motor neurons
(Figure 1). The pair of ALM cells and the AVM cells
are the sensory neurons that sense head touch, while
the pair of PLM cells are the sensory neurons respon-
sible for sensing tail touch. The simultaneous stimu-
lation of these neurons results in the reversal response
seen following tap. These touch sensory neurons syn-
apse onto the anterior ventral command interneurons
(AVD, AVB, and AVA) and the posterior ventral com-
mand interneuron (PVC), which process information
and project to appropriate motor neurons. The site of
plasticity within the neural circuit for the response to
tap is proposed to be at the glutamatergic synapses
between the mechanosensory neurons and the com-
mand interneurons. Upon repeated administration of
tap, worms habituate as measured by the decrease in
their reversal lengths after each subsequent tap.
Short-Term Memory for Habituation
C. elegans can demonstrate both short-term memory
and long-term memory (LTM) for habituation to tap.
Short-term habituation is induced by administering
30 stimuli at a 10 or 60 s interstimulus interval
(ISI), followed by testing for spontaneous recovery
414 Learning and Memory in Invertebrates: C. Elegans

Sensory neurons
Interneurons Tail
Head Command interneurons
Motor neurons

Nerve ring
Amphid sensillum

Thermosensation Chemosensation Mechanosensation

AFD ASE AWA ALM AVM PLM

AIY AIZ

RIA

RIB
RIM

PVC AVD

AVB AVA

AVE
B A

Forward Backward

Figure 1 Schematic diagram of the main components of the neural circuits that mediate mechanosensory, chemosensory, and
thermosensory behaviors that have been studied in learning and memory paradigms in C. elegans. Chemical synaptic connections are
represented by lines with arrowheads, while electrical gap junctions are represented by lines terminating in ovals. From Giles AC, Rose
JK, and Rankin CH et al. (2006) Investigations of learning and memory in Caenorhabditis elegans. Neurobiology of C. elegans.
International Review of Neurobiology 69: 37–71.

at 30 s, 5 min, and 10 min after delivery of the last
tap. Short-term habituation differs depending upon
the ISI used (Figure 2). Short ISI produce deep levels
of habituation that show rapid spontaneous recov-
ery, whereas long ISI produce intermediate levels of
habituation that show slower spontaneous recovery.
These behaviorally different forms of short-term habit-
uation are hypothesized to correlate with multiple
molecular forms of short-term memory.
Genes involved in short-term habituation Thus far,
four genes have been shown to be important for short-
term habituation to tap: eat-4, encoding a homolog of
the mammalian glutamate vesicular transporter,
VGlut1; cat-2, encoding a homolog of the mammalian
tyrosine hydroxylase; dop-1, encoding a homolog
of the mammalian type 1 dopamine receptor; and
hab-1, whose gene product has yet to be identified.
The eat-4 mutant worms show normal response to tap

2.5 10 s interstimulus interval
X Reversal magnitude (mm)
2.0
1.5
1.0
0.5
0.0
0 20
Stimuli
2.5 60 s interstimulus interval
X Reversal magnitude (mm)
2.0
1.5
1.0
0.5
0.0
0 20
Stimuli
Figure 2 Habituation of mean response amplitude (reversal
length in millimeters) to 40 tap stimuli delivered at a 10 s (top)
and a 60 s (bottom) interstimulus interval (ISI). Habituation to
stimuli presented at short ISS (10 s) produces greater levels of
habituation and a more rapid decrement of the response than
does habituation to stimuli presented at longer ISS (60 s).
but habituate in a more rapid manner and to a deeper
level than do wild-type worms. They also show slower
spontaneous recovery and interestingly do not show
dishabituation. This suggests that presynaptic release
of glutamate from the mechanosensory neurons is
vital for wild-type short-term habituation. Both cat-
2 and dop-1 mutant worms habituate more quickly
and deeply than do wild-type worms when response is
measured by the number of animals reversing to tap,
but not when measured by reversal length. This may
suggest that dopamine modulates the balance between
the head touch circuit and the tail touch circuit and
perhaps is not directly involved in the mechanism
responsible for habituation. Worms with mutations
in HAB-1 are reported to habituate more slowly than
do wild-type worms but show normal response to tap
and dishabituation. This mutation is interesting, as it
appears to have the opposite phenotype from all the
other known mutations affecting short-term habitua-
tion to date.
LTM for Habituation
LTM for habituation in C. elegans can last for as long
as 48 h, is protein synthesis dependent, and is induced
Learning and Memory in Invertebrates: C. Elegans 415
by spaced training. The protocol for spaced training
in C. elegans that induces LTM consists of four blocks
of 20 taps administered at a 60 s ISI with a 1 h rest
period between each training block (Figure 3(a)).
Worms that receive this spaced habituation training
show significantly smaller mean reversal lengths com-
pared to untrained control worms 24–48 h after the
last training session. Massed training (the same num-
ber of stimuli as in spaced training, but no rest is given
between blocks), on the other hand, does not induce
40 LTM for habituation.
Genes involved in LTM for habituation Several
genes involved in glutamate transmission that are
found at the proposed site of plasticity have been
investigated for their role in LTM in this system:
eat-4, encoding a glutamate vesicular transporter
homologous to mammalian VGlut1; glr-1, encoding a
homolog to a mammalian kainate/a-amino-3-hydroxy-
5-methyl-4-isoxazole propionic acid (AMPA)-type
glutamate receptor subunit, and nrm-1, encoding a
homolog to the mammalian N-methyl-D-aspartate
40 (NMDA)-type glutamate receptor subunit. The eat-4
and glr-1 mutant worms are deficient for forming LTM
of habituation, but, interestingly, worms do not appear
to require NMDA-type glutamate receptors for mem-
ory formation, as nmr-1 mutant worms show normal
LTM (Figure 3(b)). Confocal imaging of transgenic
worms expressing GLR-1 fused to a green fluorescent
protein (GFP) and quantitative reverse transcriptase
polymerase chain reaction (RT-PCR) have shed some
light on the functional importance of GLR-1. When
measured 24 h after spaced training, GLR-1 expression
levels are observed to decrease; suggesting that LTM
for habituation is molecularly mediated by a down-
regulation of GLR-1 expression (Figure 3(c)).
Context Associations with Habituation to Tap
C. elegans is also capable of forming chemosensory
context associations with habituation to tap. When
worms plated on agar treated with Naþ (taste worms
are attracted to) are habituated with 30 taps at a 10 or
a 60 s ISI, then are transferred onto plain agar for a 1 h
rest period and, finally, rehabituated on Naþ-treated
agar, they show greater retention of the earlier train-
ing (demonstrated by smaller reversal lengths in the
second round of habituation) than do worms that
were trained and tested on plates without the Naþ
taste. This form of associative conditioning has been
shown sensitive to extinction (you do not see this
effect if you leave the worms in the same context that
they are trained and tested in for the 1 h rest period)
and latent inhibition (preexposure to the context for
1 h before training diminishes the context effect).
416 Learning and Memory in Invertebrates: C. Elegans

Trained 20 20 20 20
taps taps taps taps
10
24 h test
taps
Control 1
tap
a

Wild-type eat-4
120 120
% Control response

% Control response
**

60 60

0 0
Mean Mean
nmr-1 glr-1
120 120
% Control response

% Control response
**

60 60

0 0
b Mean Mean

Control

c Trained

Figure 3 Long-term memory (LTM) paradigm and corresponding genetic analysis. (a) Protocol for spaced training in C. elegans that
induces LTM. Trained worms receive four blocks of 20 taps administered at a 60 s ISI with a 1 h rest period between each training block,
while control worms receive one tap. After 24 h, ten taps are administered to both control and trained worms to test for memory. Memory is
seen when trained worms show significantly smaller responses than do control worms. (b) Mean reversal lengths of wild-type worms and
of eat-4, nmr-1, and glr-1 mutants during the ten test taps, 24 h after training, measured as a percentage of control reversal lengths for
trained and control worms. Wild-type and nmr-1 mutants show normal LTM, whereas eat-4 and glr-1 do not. (c) Fluorescent imaging of a
GLR-1–GFP fusion protein 24 h after LTM training in trained and untrained control worms. GLR-1 expression levels are observed to
decrease for trained worms. Scale bar ¼ 20 mm.

Chemosensory Learning and Memory
Worms are attracted and migrate toward cations,
anions, cyclic nucleotides, and volatile chemicals; this
behavior is termed chemotaxis (Figure 4). Chemotaxis
is usually measured through either one of two com-
mon assays: the first is orientation, quantified by
tracking the path of individual worms as they migrate
toward or away from a chemical, and the second
is accumulation, quantified by counting the number
of worms that collect at the location of the chemical.
This behavior has been found subject to several forms
of learning in C. elegans: habituation to low levels of
odorants, state-dependent adaptation to high levels of
odorants, classical conditioning, and aversive learning.
The neural circuit that mediates chemotaxis has
been mapped (Figure 1) and consists of many more
sensory neurons than do the other behaviors dis-
cussed in this article. In total, 11 pairs of sensory
neurons in the head region of the worm are respon-
sible for chemotaxis. Eight pairs have sensory endings
that are in contact with the external environment and
for the most part detect water-soluble attractants.
The additional three pairs are enclosed in the amphid
sheath and their main role is to detect volatile chemicals.
Because these 11 pairs of neurons respond to such a
large number of different chemical substances, it is
thought that single chemosensory neurons are capable
of detecting multiple chemicals, and, further, this
 Learning and Memory in Invertebrates: C. Elegans 417

Training Testing

Stimulus
Chemotaxis No preexposure
Control

Dishabituating
Adaptation stimulus*
and Preexposure
habituation to stimulus

State-
dependent
Preexposure cue absent
State-dependent to stimulus
learning and state-
dependent cue
State-
dependent
cue present

CS+ and US CS− alone

CS+
Classical
conditioning
CS−

Figure 4 Schematic diagram of chemotaxis and the adaptation, habituation, state-dependent learning, and classical conditioning
paradigms. In chemotaxis, worms migrate toward an attractive odor (green) such as diacetyl, rather than to a control stimulus (blue) such
as water. Adaptation and habituation are produced by preexposing worms to an attractive chemical stimulus for an extended period of
time. When worms are later tested for chemotaxis they no longer show a preference for that chemical over a control chemical. Adaptation
is induced by exposing worms to high concentrations of the stimulus, whereas habituation to Naþ or diacetyl is induced by exposure low
concentrations. Once worms are habituated to Naþ or diacetyl they can be dishabituated* by exposing them briefly to a high concentration
of that chemical; this does not occur for adaptation. In the paradigm for state-dependent learning starved or inebriated worms are
preexposed to an odor and learn to associate this odor with their physiological state. Thus, when worms are later exposed to that odor they
only show adaptation when they are in the same physiological state as when they were preexposed. In the differential classical
conditioning paradigm worms are first preexposed to an odor (conditioned stimulus, CSþ; green) in the presence of food (unconditioned
stimulus, US) and then preexposed to another odor without food (CS; red). When worms are later placed in the presence of both odors
they show a preference for the odor that was previously paired with food (CSþ).

suggests that one site of plasticity for chemotaxis behav-
ior may be intraneuronal.
Adaptation
Adaptation, a decrease in responding after lengthy
exposure to a stimulus (i.e., no longer noticing an
odor after a long exposure to it), itself is not consid-
ered learning; however, it can have associations
formed so that it plays a role in associative learning
in experiments of state dependency. In the adaptation
paradigm worms are exposed to a high concentration
of a particular odorant for a determined period, called
the adaptation period. After the worms are moved to a
chemotaxis assay plate (test odorant on one side and a
control substance on the other) (Figure 4), the chemo-
taxis index ((number migrated to test  number
migrated to control)/total number) is measured.
State-dependent learning C. elegans can show state-
dependent learning – that is to say, they can make
associations between their physiological state and
stimuli in their environment (Figure 4). Worms can
associate a feeding state or an inebriated state,
induced by ethanol, with adaptation to an odor.
When starved worms are preexposed to odor, in this
case benzaldehyde, they show greater adaptation to
that odor than do unstarved control worms. When
worms are preexposed to the odor in the presence of
an excess of food, they show less adaptation than
do control worms. The neurotransmitter serotonin,
which is known to be important in other feeding-
state-dependent behaviors, has been shown to mediate
this feeding-state-dependent association. Similar to
the feeding-state experiments, inebriated worms pre-
exposed to an odor only show adaptation to that odor
418 Learning and Memory in Invertebrates: C. Elegans
when they are tested in the presence of inebriating
doses of ethanol.
Habituation
Habituation to some chemosensory stimuli can also
be observed in C. elegans. Preexposure to weak con-
centrations of either Naþ or diacetyl causes the
worms to habituate to that chemical; this can be
observed as a decreased percentage of worms migrat-
ing in the direction of the chemical stimulus. This
habituation can be differentiated from adaptation
by the application of a dishabituating stimulus, a
short exposure to a higher concentration of the chemi-
cal. This brief exposure immediately reverses the
behavior such that an increase in the percentage of
worms migrating in the direction of the weak concen-
tration of the chemical stimulus is seen (Figure 4).
This does not occur for adaptation. Whether worms
habituate to either Naþ or diacetyl or adapt to these
chemical stimuli is determined by the concentration
of the chemical. Habituation is seen at low concen-
trations of these chemicals, whereas adaptation is
seen at higher concentrations.
Classical Conditioning
Differential classical conditioning, a form of associa-
tive learning, has been shown to exist in C. elegans.
The first paradigm used to investigate this type of
learning consisted of preexposing worms to two
odors and pairing one odor with (conditioned stimu-
lus; CSþ) and the other odor without (CS) food.
After training, worms placed on a test plate that
contain both the CSþ and CS odors significantly
preferred the odor which had been paired with food
(Figure 4). Differential classical conditioning can also
be demonstrated by pairing an aversive stimulus, such
as garlic, with the CSþ odor. In this paradigm worms
significantly prefer the CS odor that was not paired
with the aversive stimulus. Since the development of
these paradigms, several others have been intoduced.
These include pairing odors with feeding states and
tastes. Thus, these studies illustrate that the small
worm with its tiny nervous system is capable of com-
plex chemosensory learning.
Genes involved in classical conditioning Several
genes identified by means of genetic screens and
behavioral investigations are important for differen-
tial classical conditioning. Two as yet unidentified
genes, lrn-1 and lrn-2, show normal chemotaxis and
chemotactic habituation but are deficient for condi-
tioning. As discussed earlier, the glutamate receptor
subunit, GLR-1, is important for LTM for habituation
to mechanosensory stimulus; the gene for this receptor
subunit has also been shown to be an important gene
for chemosensory learning: glr-1 mutants show defi-
ciencies for both chemotactic habituation and differen-
tial classical conditioning. Last, mutations in the gene
hen-1, whose gene product is a low-density lipoprotein
(LDL) receptor-like secretory protein, lead to abnormal
sensory integration of chemosensory signals and no
observed learning.
Aversive Learning
One of the most recent forms of learning discovered
in C. elegans is the capacity to modify its chemo-
sensory preferences after being exposed to pathogenic
bacteria. This means that C. elegans can learn to
avoid odors or tastes associated with familiar patho-
genic bacteria and in turn increase its preference for
odors or tastes associated with familiar nonpatho-
genic bacteria. In this paradigm, worms were placed
on pathogenic bacteria for 4 h and subsequently for
4 h on nonpathogenic bacteria. This was followed by
a choice test whereby half of the agar plate contained
the pathogenic bacteria and the other half contained
the nonpathogenic bacteria. Worms were observed to
avoid the pathogenic bacteria and were attracted
to the nonpathogenic bacteria. This study also identi-
fied serotonin and the gene mod-1, the gene product
of which is a serotonin-gated chloride channel, as
important components to this behavior.
Thermotactic Learning and Memory
Behavioral plasticity has also been shown in
C. elegans for thermotactic behavior. Thermotaxis is
defined as movement toward or away from a thermal
stimulus. Worms can learn to associate a particular
temperature with the presence or absence of food.
This can be measured by placing the worms on a tem-
perature gradient; if the worms have recently been well
fed in an environment at a constant temperature they
will migrate to this temperature when placed on the
gradient (Figure 5). Conversely, if the worms have
recently experienced starvation at a constant tempera-
ture they will avoid this temperature when placed on the
gradient. This behavior is termed isothermal tracking.
The circuit that mediates thermotaxis has been
mapped and consists of one pair of anterior sensory
neurons (AFD) in the head region that project to several
anterior interneurons (AIY, AIZ, and RIA) which com-
pute the information (Figure 1). Through laser ablation
experiments it has been demonstrated that AIY may
signal for thermotaxis to warmer temperatures, while
AIZ may signal for thermotaxis to cooler temperatures.
These two interneurons converge onto RIA, which
is proposed to be a site of thermotactic integration.

Isothermal
tracking Athermotactic
25 ⬚C 25 ⬚C
15 ⬚C 15 ⬚C
tax-2
Wild type
tax-4
Cryophilic Thermophilic
25 ⬚C 25 ⬚C
15 ⬚C
15 ⬚C
ttx-3
lin-11
nsc-1
Figure 5 Schematic representation showing wild-type thermo-
tactic behavior (isothermal tracking) and the various mutant phe-
notypes observed when mutations affect thermotactic behavior.
Athermotactic phenotypes show no preference for any tempera-
ture. Cryophilic phenotypes show a preference for cooler tem-
peratures than the temperature that was previously paired with
food. Thermophilic phenotypes show a preference for warmer
temperatures than the temperature that was previously paired
with food. Adapted from Giles AC, Rose JK, and Rankin CH
(2006) Investigations of learning and memory in Caenorhabditis
elegans. Neurobiology of C. elegans. International Review of
Neurobiology 69: 37–71.
The site of plasticity within the neural circuit for
thermotaxis is proposed to lie within the AFD sensory
neurons and the AIY interneuron.
Parsing Thermotactic Learning into
Its Components
After worms learn the association of a temperature
with a presence or absence of food, this memory is not
resistant to future modifications, as the associated
temperature can be ‘reset.’ Worms raised at a par-
ticular cultivation temperature with food show a
preference for that temperature when placed on a
temperature gradient, as stated earlier, but this
association with food can be transferred to another
temperature if the cultivation temperature is shifted
to the new temperature in the presence of food.
This isothermal tracking can be parsed into two
components: the response to a temperature shift and
the change in behavior due to the presence of food.
This is accomplished by observing how long it takes
Learning and Memory in Invertebrates: C. Elegans 419
worms to learn a new temperature or feeding state
after having already committed this type of associa-
tion to memory. When worms are switched from their
cultivation temperature to a new temperature, it takes
them 2–3 h to learn this new association, and this
learning is temperature independent. When worms
are transferred to a different feeding state under the
same temperature, they learn this new association in a
temperature-dependent fashion. When they are trans-
ferred from a nutrient-rich to a nutrient-poor environ-
ment at cooler temperatures (17  C), they are capable
of learning the new association after 3 h, whereas at
warmer temperatures (25  C) it takes them only
30 min to make this new association. When they are
transferred from a nutrient-poor to a nutrient-rich
environment, they are able to learn this association
in under 10 min. Similar results are seen when a
double switch of temperature and feeding state are
performed. This suggests that the environmental tem-
perature is encoded through a relatively long process,
while a relatively short process encodes the pairing of
the feeding state to the stored temperature.
The roles that different neurotransmitters play in
thermotaxis have been investigated to further dissect
the two components of this behavior. The neurotrans-
mitter serotonin is proposed to mimic a well-fed state
in C. elegans, and an exogenous application of this
neurotransmitter to starved worms during condition-
ing to a temperature mimics the effect of a food-rich
environment, meaning that when they are placed on a
temperature gradient they thermotax to the tempera-
ture at which serotonin was applied. The neurotrans-
mitter octopamine is thought to mimic a starved state
in C. elegans, and when exogenous octopamine is ap-
plied to well-fed worms during cultivation, worms
later avoid the cultivation temperature when placed
on a temperature gradient. This evidence supports the
hypothesis that these neurotransmitters play a role in
the associative learning for thermotaxis.
Genes Involved in Thermotactic Learning
and Memory
Investigations into this behavioral plasticity have
begun to identify some of the genes involved in thermo-
tactic behaviors. The original mutant screens develop-
ed to identify genes important for thermotaxis
grouped positive mutants into one of three pheno-
typic categories: thermophilic, worms which migrate
to temperatures that are higher than their cultiva-
tion temperatures; cryophilic, worms which migrate
to temperatures that are lower than their cultivation
temperatures; and athermotactic, worms which show
no preference for any temperature. This screen identi-
fied a plethora of mutants with thermotactic deficits,
420 Learning and Memory in Invertebrates: C. Elegans
such as tax-2, tax-4, ttx-3, and lin-11, which have
mutations in genes that encode cyclic nucleotide-
gated channels and transcription factors (Figure 5).
To investigate mutants defective for forming asso-
ciations between temperature and food a genetic
screen was done that looked for worms abnormal
for updating their isothermal tracking. From this,
three mutants, aho-1, aho-2, and aho-3, were identi-
fied. These mutants show normal thermotaxis when
they are cultivated in a well-fed state, but they cannot
learn to avoid the cultivation temperature if they are
conditioned in a starved state. The deficit exhibited
by these mutants implies that these mutations inter-
fere with associating the encoded temperature with
the feeding state, but does not interfere with the
encoding of the temperature itself. Thus, on top
of identifying genes involved in this learning para-
digm, this screen also illustrates that the two aspects
of thermotaxis exist (the thermal memory and the
associative learning).
Several other genes implicated in thermotaxis have
been also been identified. One such gene encodes
neuronal calcium sensor-1 (NCS-1); ncs-1 mutants
perform cryophilically on the thermotactic learning
assay. Selective rescue of NCS-1 in the AIY inter-
neuron led to a full behavioral recovery. Rescue of
NCS-1 in AIY with a transgene containing a point
mutation in the calcium-binding region did not result
in a behavioral recovery, suggesting that intracellular
calcium signaling in the AIY interneuron may be impor-
tant for thermotactic learning. Lastly, hen-1 (shown to
play a role in chemosensory learning) is also involved in
thermotaxis learning. Mutants deficient for this gene
will migrate to their cultivation temperature indepen-
dent of the feeding state with which it was previously
paired. The involvement of HEN-1 in both chemosen-
sory and thermotactic learning provides support for a
role of this protein in general sensory integration.
Conclusion
Investigations into behavioral plasticity in C. elegans
have demonstrated that this simple worm is capable
of many forms of learning and memory in a variety of
sensory modalities. Simple forms of learning include
chemosensory and mechanosensory habituation and
dishabituation. The complex learning behaviors
exhibited by the worm include classical conditioning,
context conditioning, state-dependent learning, and
aversive learning. Several important genes for these
behaviors have already been identified and investiga-
tions into identifying other genes continue, as do
studies attempting to link the molecular mechanisms
responsible for learning and memory.
This rich learning and memory repertoire exhibited
by C. elegans along with its mapped nervous system
and fully sequenced genome make it an ideal inverte-
brate model organism to study learning and memory.
Other advantages to using C. elegans for this are
the plethora of mutants available for analysis, the
increasing number of fluorescent fusion proteins for
studying protein localization and function, and
homology between worms and higher organisms.
These all suggest that important findings on learning
and memory of general interest are possible and very
likely using the worm as a model system.
See also: Conditioning: Theories; Cyclic AMP (cAMP) Role
in Learning and Memory; Long-Term Potentiation (LTP):
Mossy Fiber cAMP-Dependent Presynaptic LTP; Operant
Conditioning of Reflexes; Procedural Learning: Classical
Conditioning.
Further Reading
De Bono M and Maricq AV (2005) Neuronal substrates of complex
behaviors in C. elegans. Annual Review of Neuroscience 28:
451–501.
Giles AC, Rose JK, and Rankin CH (2006) Investigations of
learning and memory in Caenorhabditis elegans. Neurobiology
of C. elegans. International Review of Neurobiology 69: 37–71.
Hobart O (2003) Behavioral plasticity in C. elegans: Paradigms,
circuits, genes. Journal of Neurobiology 54: 203–223.
Mohri A, Kodama E, Kimura KD, et al. (2005) Genetic control
of temperature preference in the nematode Caenorhabditis
elegans. Genetics 169: 1437–1450.
Mori I (1999) Genetics of chemotaxis and thermotaxis in the
nematode Caenorhabditis elegans. Annual Review of Genetics
33: 399–422.
Rankin CH (2002) From gene to identified neuron to behavior in
Caenorhabditis elegans. Nature Reviews Genetics 3: 622–630.
Rankin CH, Beck DO, and Chiba CM (1990) Caenorhabditis
elegans: A new model system for the study of learning and
memory. Behavioural Brain Research 37: 89–92.
Riddle DL, Blumenthal T, Meyer BJ, et al. (1997) C. elegans. II.
Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
Rose JK and Rankin CH (2001) Analyses of habituation in
Caenorhabditis elegans. Learning & Memory 8: 63–69.
Steidl S, Rose JK, and Rankin CH (2003) Stages of memory in the
nematode Caenorhabditis elegans. Behavioral and Cognitive
Neurosciences Review 2: 3–14.
Wood WB (1988) The Nematode Caenorhabditis elegans. Cold
Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
Zhang Y, Lu H, and Bargmann CI (2005) Pathogenic bacteria
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Relevant Websites
http://elegans.swmed.edu – Caenorhabditis elegans World Wide
Web server (University of Texas, Southwestern Medical Center).
http://www.wormbase.org – WormBase (Cold Spring Harbor
Laboratory, Cold Spring Harbor, NY).