|
| |
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online February 15, 2006
Journal of Experimental Biology 209, 826-833 (2006)
Published by The Company of Biologists 2006
doi: 10.1242/jeb.02069
Taste discrimination in conditioned taste aversion of the pond snail Lymnaea stagnalis
1 Division of Biological Sciences, Graduate School of Science, Hokkaido
University, North 10, West 8, Kita-ku, Sapporo 060-0810, Japan
2 Laboratory of Functional Biology, Faculty of Pharmaceutical Sciences at
Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki 769-2193,
Japan
3 Department of Physiology, School of Medicine, Sapporo Medical University,
South 1, West 17, Chuo-ku, Sapporo 060-8556, Japan
4 Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N
4N1, Canada
5 Division of Innovative Research, Creative Research Initiative
"Sousei" (CRIS), Hokkaido University, North 21, West 10, Kita-ku,
Sapporo 001-0021, Japan
* Author for correspondence (e-mail: eito{at}sci.hokudai.ac.jp)
Accepted 3 January 2006
 |
Summary |
|---|
 TOP Summary IntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Key words: conditioned taste aversion, long-term memory, Lymnaea stagnalis, second-order conditioning, taste discrimination
|
Introduction |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
; Jones et al.,
2003; Lukowiak et al.,
2003; Fulton et al.,
2005; McComb et al.,
2005a; McComb et al.,
2005b; Parvez et al.,
2005; Sakakibara et al.,
2005). Our team has studied another form of classical conditioning
and its consolidation into long-term memory, namely conditioned taste aversion
(CTA) (Ito et al., 1999). To
produce CTA in Lymnaea, an appetitive stimulus (e.g. sucrose) is used
as the conditional stimulus (CS). Application of CS to the lips increases the
feeding response in snails. An aversive stimulus (e.g. KCl) is used as the
unconditional stimulus (US). Application of US to the snail inhibits feeding
behavior. In CTA training, the CS is paired with the US. After repeated
temporal contingent presentations of the CS and US, the CS no longer elicits
feeding response (i.e. the new behavioral response), and this aversive
conditioning persists as a long-term memory
(Kojima et al., 1996;
Kawai et al., 2004). In
Lymnaea, an identifiable neuron, known as the cerebral giant cell,
has been hypothesized to be the key neuron for both the acquisition and
formation of long-term memory of CTA
(Kojima et al., 1997;
Nakamura et al., 1999a;
Kojima et al., 2001).
To begin to elucidate the cellular and molecular mechanisms underlying: (1)
the acquisition of CTA, and (2) the consolidation of learning into long-term
memory persistence, we have employed a number of different procedures
utilizing techniques directed against specific molecules in snails
(Kobayashi et al., 2000a;
Kobayashi et al., 2000b;
Hatakeyama et al., 2004a;
Hatakeyama et al., 2004b;
Hatakeyama et al., 2004c). For
the formation and maintenance of long-term memory following CTA training, a
molecular cascade is necessary in the cerebral giant cells, involving cyclic
AMP (cAMP), protein kinase A and cAMP responsive element binding protein
(CREB) (Nakamura et al.,
1999b; Ribeiro et al.,
2003; Sadamoto et al.,
2004a; Sadamoto et al.,
2004b; Wagatsuma et al.,
2005).
However, in our studies designed to determine how long the long-term memory
for the CTA persists, it became apparent that snails continued to eat their
normal diet of lettuce in their home aquaria while still having a memory for
the CTA. Thus, it was unclear what the relationship was between CTA for a
specific CS and other appetitive food stimuli. In other words, what capacity
do snails have to differentiate between appetitive food stimuli during
training and testing for long-term memory so that they can avoid one food type
(i.e. CTA) whilst continuing to be attracted to another? Moreover, if they can
successfully differentiate between appetitive food stimuli, where in the
central nervous system does this occur? Lymnaea certainly have been
shown to possess the capacity to distinguish between food types; in appetitive
conditioning, they can differentiate between appetitive food stimuli
(Straub et al., 2004), whereas
in an operant conditioning procedure they can differentiate a carrot stimulus
from other stimuli (Haney and Lukowiak,
2001; Sangha et al.,
2005).
In the present study, we directly demonstrate that snails can be differentially conditioned to avoid one appetitive CS following CTA training whilst continuing to be responsive to another different appetitive food CS that has not been paired in a forward manner with an aversive US. In addition, we also found during the course of our studies that Lymnaea have the capability of undergoing second-order conditioning.
|
Materials and methods |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
; McComb et al.,
2005b) were obtained from our snail-rearing facility (original
stocks from Vrije Universiteit Amsterdam supplemented with snails from the
Calgary facility, which were also derived from the same Amsterdam colony). All
snails were maintained in dechlorinated tapwater (i.e. pondwater) and fed
lettuce on a 12 h:12 h L:D cycle at 20–24°C.
Conditioning procedures for conditioned taste aversion
Before conditioning, snails were starved for 1 day. Then, the snails were
trained by a CTA procedure in a 60 mm Petri dish. The CS was either a 5 ml
solution of 10 mmol l–1 sucrose or a solution of 0.3% carrot
juice, whereas the US was a 5 ml solution of 10 mmol l–1 KCl.
One of the CSs and the US were pipetted into a Petri dish for 15 s with a 15 s
inter-stimulus interval. This pairing of CS and US was repeated 10 times with
a 10 min inter-trial interval. Before and after the training session, a 5 ml
solution of the CS was applied to the lip and washed out with distilled water.
The feeding response elicited by the CS (i.e. bites min–1)
was determined for a 1-min interval. We compared the feeding response before
training (pre-test) to the feeding response following training (post-test). A
backward-conditioned (the US precedes the presentation of the CS) control
group and a naive (distilled water only applied to the lips instead of the CS
and US) control group were also employed.
Conditioning procedures for second-order conditioning
We used the following training procedure to determine if Lymnaea
were capable of undergoing second-order conditioning. The two appetitive CSs
described above (sucrose and carrot juice) and the aversive US (KCl) were
used. To determine if snails had the capacity to undergo second-order
conditioning, we used a two-phase training procedure. In the first phase,
snails were conditioned as previously described, and so the first-order CTA
was established. Snails were conditioned to avoid one of the appetitive food
substance (CS1) by pairing CS1 with the US. In the second phase, the other CS
(CS2) was used and paired in a forward manner with the CS1, and so the CS1 now
served as the US. If snails are capable of undergoing second-order
conditioning, CS2 should no longer act as an appetitive stimulus, rather it
acquires the ability to evoke CTA, even though it was never paired with the US
(Carew and Sahley, 1986). In
the present study, the CS1 (e.g. sucrose) was paired with the US 10 times, and
then the CS2 (e.g. carrot juice) was paired with the CS1 10 times. The
inter-stimulus interval and inter-trial interval were the same as those in the
CTA training procedure first described above. We also performed the
experiments using carrot juice as the CS1 and sucrose as the CS2.
The entire training and testing procedures were performed under a blind protocol. In the post-test, the good performers were defined as those snails responding to the CS with 0 or 1 bite min–1; whereas the poor performers were those snails responding to the CS with 2 or more bites per minute.
Statistical analyses
Data are expressed as means ± s.e.m. Statistical significance
(P<0.05) was determined by one-way analysis of variance (ANOVA)
followed by the post hoc Scheffé test and Student's
t-test.
|
Results |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
|
Conditioned taste aversion experiments
Snails were trained on the basis of the 10-trial training (i.e. CS–US
pairing) procedure described in the Materials and methods. As a CS, we used
either 10 mmol l–1 sucrose or 0.3% carrot juice. A 10 mmol
l–1 KCl solution was used as the US. We also prepared naive
and backward-conditioned snails as controls. In all cohorts of snails, a
pre-test to the specific CS (either sucrose or carrot juice) was given and the
number of bites min–1 ascertained. We first examined whether
sucrose could be used as the CS in these experiments. Thus the sucrose CS was
paired with the US. Following CTA training, we found that the feeding response
elicited by sucrose in the post-test session was significantly reduced
(P<0.01, one-way ANOVA followed by the post hoc
Scheffé test) compared to both the pre-test session and to the
post-test session of the backward-conditioning control or the naive control
group (Fig. 2A). Moreover in
all cases, there were no significant differences (P>0.05) in the
feeding responses elicited in the pre-test session of the CTA-trained cohorts,
backward-conditioning control or naive control snails.
|
Taste discrimination and memory retention in conditioned taste aversion
To directly determine if Lymnaea are capable of discriminating
between the two appetitive stimuli (sucrose solution and carrot juice) used in
CTA training, we first used the 10 mmol l–1 sucrose solution
as the CS(+) and the 0.3% carrot juice as the CS(–). We then performed
experiments using carrot juice as the CS(+) and sucrose as the CS(–). In
all these experiments, both the CS(+) and the CS(–) were given to all
snails. Moreover in the pre-test session (i.e. before any training), both the
CS(+) and CS(–) induced a similar robust feeding response. However,
after the CS(+) was paired 10 times with the US (the KCl stimulus), the CS(+)
no longer elicited a robust feeding response. The feeding response elicited by
the CS(+) in the post-test session given 48 h after training was significantly
smaller than the response in the pre-test session (P<0.01,
Student's t-test, Fig.
3A). By contrast, the feeding response elicited by the CS(–)
in the post-test session 48 h after training was statistically not different
(P>0.05) from the response elicited in the pre-test session
(Fig. 3A).
|
Second-order conditioning
Whereas second-order conditioning has been demonstrated previously in the
terrestrial slug Limax maximus
(Sahley et al., 1981), to our
knowledge only the sensory preconditioning has been demonstrated in
Lymnaea (Kojima et al.,
1998). We therefore examined whether or not second-order
conditioning is possible using two appetitive CSs (sucrose and carrot juice)
described above. In the first series of experiments, we used the 10 mmol
l–1 sucrose solution as the CS1 and the 0.3% carrot juice as
the CS2; the 10 mmol l–1 KCl solution continued to be used as
the US (Fig. 4A). In the first
phase of training, the CS1 and the US were paired 10 times. In the second
phase of training, the CS2 was then paired with the CS1 10 times.
|
We then tested whether or not the feeding response to CS2 (carrot juice) in the final test session was significantly reduced (P<0.01, Student's t-test) compared to the response elicited in the pre-test session. However, whereas carrot juice (CS2) elicited significantly fewer bites in the final test session that it did in the pre-test session, it still elicited significantly more bites (P<0.01, Student's t-test) than did sucrose (CS1). The CS1 thus suppressed the feeding response to a significantly greater extent than did the CS2 after the pairing of the CS2 with the CS1.
We obtained statistically similar results when we used carrot juice as the CS1 and sucrose as the CS2 (Fig. 4B). We can therefore draw two conclusions from these data. First, second-order conditioning is possible in Lymnaea. Second, even after second-order conditioning, snails are still capable of discriminating between the two CSs.
Extinction of conditioned taste aversion memory
Whereas extinction of a learned and remembered operantly conditioned
behavior in Lymnaea has previously been demonstrated
(Sangha et al., 2003), to our
knowledge extinction of a learned and remembered CTA has not been
demonstrated. We therefore attempted to extinguish CTA. To determine if we
could extinguish a CTA, we first trained snails as described. We thus paired
the sucrose CS with the KCl US, and this produced CTA
(Fig. 5A). Following the
learning, we presented the CS alone (i.e. it was not paired with the US) three
times at 10 min intervals (i.e. 10 min, 20 min and 30 min after the end of
conditioning procedure). At each presentation of the CS alone (equivalent to a
memory test), we measured the number of bites elicited by the CS.
|
As can been seen, the memory for CTA was not extinguished. The number of bites elicited by the sucrose CS following the attempted extinction procedure was still significantly less (P<0.01, Student's t-test) in each of the CS alone sessions and also in each of the post-test sessions (up to 24 h after training). In addition, even when we separated out the so-called good and poor performers (see Materials and methods), extinction did not occur. Moreover, the difference between the feeding responses elicited by the CS following training and attempted extinction between good and poor performers continued to be maintained.
Finally, when carrot juice was used as the CS (Fig. 5B), the data we obtained were similar to those obtained with sucrose. Thus, we conclude that the CTA memory is not extinguished by the repetitive conditional stimuli.
|
Discussion |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Taste discrimination system existing before memory formation
We first showed that different food tastes elicit different levels of
feeding, as assessed by the number of bites elicited by the food taste to the
lip area of the snail (Fig. 1).
For both sucrose and carrot juice, there was the expected dose–response
curve with increasing concentrations of the food substance eliciting a larger
feeding response. In contrast, the response elicited by glutamate was
different in two respects. First, glutamate did not elicit a robust feeding
response, as compared to both sucrose and carrot juice, and second its
dose–response was a U-shaped curve. Higher concentrations actually
elicited a weaker feeding response. Puzzling also was the fact that the
combination of glutamate and sucrose did not result in an additive
response.
Where and how (i.e. the neural basis of food discrimination) taste
discrimination occurs is not certain in Lymnaea, although a recent
paper (Straub et al., 2004)
presents compelling data that the output from peripheral sensory neurons in
the lip area is not significantly altered following appetitive conditioning,
suggesting that taste discrimination does not occur peripherally. Future
experiments will have to address this question. The results from these initial
experiments allowed us to choose appropriate concentrations of different food
stimuli that elicit comparable levels of feeding in naive snails. Thus we were
able to test taste discrimination following CTA training.
Having shown that two different tastes elicited robust feeding responses,
we had to ascertain whether or not each specific taste could undergo CTA. We
found that CTA produced by pairing either sucrose or carrot juice with the
suppressive KCl stimulus was similar (Fig.
2). Previously, our group had only used sucrose for CTA
(Kojima et al., 1996;
Kojima et al., 1997;
Wagatsuma et al., 2004). Thus
Lymnaea can learn and remember to avoid different food tastes.
Whereas similar findings were found previously in Limax
(Sahley et al., 1981), this is
the first time it has been demonstrated in our Lymnaea model
system.
After acquiring and committing to memory a CTA for a specific food taste, we found that snails have the capacity to discriminate between that taste and a different taste (Fig. 3). The feeding response elicited by the safe taste (i.e. the taste not paired with the KCl aversive stimulus) in CTA-trained snails was similar to that elicited by the taste in naive snails. Either of the two tastes we employed in our experiments could serve as the conditioned or the safe taste. Thus, CTA training did not appear to alter the ability of a safe taste to elicit a feeding response.
These results suggest that the loci for taste discrimination occur upstream
from the site of CTA memory formation and storage. Previously, Kojima et al.
(Kojima et al., 1997;
Kojima et al., 2001) proposed
a neuronal model for CTA. In their model the cerebral giant cells played a
pivotal role in CTA. Activity in the cerebral giant cells was hypothesized to
suppress the activity of the central pattern generator that drives feeding
behavior. This suppression was thought to be due to the enhancement of
inhibitory postsynaptic potentials from the cerebral giant cells to the
central pattern generator that drives feeding in the conditioned snails
(Kojima et al., 1997;
Kojima et al., 2001). The data
that we have obtained here, namely the ability to discriminate food tastes
after CTA, are not consistent with the predictions of the Kojima model. As the
model was presented following CTA, a different food taste should not have been
able to elicit a feeding response since for all effective purposes, the
central pattern generator that drives feeding behavior could not have been
activated according to the Kojima model. Clearly as our data show this is not
the case. Thus we must now modify the Kojima model.
However, the necessity of modifying the Kojima model does not mean that the
cerebral giant cells play no role or only a minor role in mediating CTA
learning and memory. What the results presented here mean is that the circuits
underlying learning and memory formation are much more complicated than we
initially envisioned. This notion that the neural basis of learning and
remembering various feeding behavior is more complicated than initially
thought is not only our view, but it is the view of others working on feeding
in Lymnaea. For example, Straub and his colleagues showed that no
change was observed in the peripheral inputs following the appetitive taste
conditioning to a food taste that initially did not activate feeding behavior
in a robust manner (Straub et al.,
2004). Their data suggest that the changes occurring at loci not
yet identified probably mediate the taste discrimination. Our data presented
here are consistent with the view expressed by Straub et al.
(Straub et al., 2004). Thus,
we must consider a mechanism for taste discrimination in the neural pathways
before the cerebral giant cells in the central nervous system.
Second-order conditioning by tastes
In the course of our experiments to show taste discrimination following
CTA, we found that it is possible to induce second-order conditioning in
Lymnaea. To our knowledge this is the first instance that
second-order conditioning has been demonstrated in Lymnaea.
Previously, this form of conditioning was demonstrated in another molluscan
preparation Limax (Sahley et al.,
1981). We are not sure if any other group has attempted to show
such higher order conditioning in other molluscan preparations. It is our
feeling that it would be possible to do so, but most probably it has not been
tried. An advantage that the Lymnaea model system may have over the
Limax model system is that the Lymnaea neural circuitry may
be a little better analyzed (e.g. Ito et
al., 2003a; Ito et al.,
2003b; Ito et al.,
2004; Fujie et al.,
2005). What the ability to demonstrate second-order conditioning
shows is that CTA is an extremely robust memory, in that the memory for one
taste that initially elicited feeding response can be used following CTA as a
negative reinforcer for a second appetitive taste. This again confirms the
extreme robustness of the CTA memory.
Rigid memory formed by conditioned taste aversion training
Extinction as famously described in early work by I. P. Pavlov is the
repeated exposure to the CS (in our case a food taste) without the
presentation of the US (the KCl stimulus)
(Mackintosh, 1974). If
extinction occurs the conditioned response (i.e. CTA) is decreased.
Importantly, extinction training has been shown to be the result of new memory
formation and does not erase the previously learned response
(Bouton, 1993). Extinction is
not unlearning, as the original memory can be shown to still be present (i.e.
the phenomenon of spontaneous recovery). There is evidence that competition
may exist between the original memory and the extinction memory
(Sangha et al., 2005). It is
not clear what mechanism(s) allows one memory to dominate over the other.
Here we demonstrated that the CTA memory was also resistant to extinction
(Fig. 5). This implies that the
CTA memory is robust. A robust and long-lasting memory is a hallmark of CTA.
In mammals, for example, CTA has been associated with gut illness
(Garcia et al., 1955), viewed
as part of a gut defense system (Garcia et
al., 1985), and formed quickly and maintained as long-term memory
(Garcia et al., 1974). Thus, it
is not too surprising that this memory is resistant to extinction training.
Further experiments will be necessary to determine what the molecular basis of
CTA memory is in Lymnaea (e.g.
Sadamoto et al., 2004a;
Sadamoto et al., 2004b;
Wagatsuma et al., 2005).
These data and consideration of the mammalian data suggest to us that we
need to incorporate feedback from the gastric system into our model in order
to consolidate the memory in the central nervous system in Lymnaea.
Because the B2 motoneurons, which control digestion, can release nitric oxide
and affect the buccal neurons (Sadamoto et
al., 1998; Kobayashi et al.,
2000a; Kobayashi et al.,
2000b), the B2 motoneurons may associate gastric malaise with
inhibition of feeding behavior, resulting in consolidation of the CTA memory
(Hatakeyama et al., 2006).
Future experiments will be designed to specifically test this hypothesis.
Interestingly, nitric oxide is involved in odor discrimination in the
associative learning of another mollusc, Limax
(Sakura et al., 2004).
In conclusion, Lymnaea can distinguish between tastes following CTA. The neurons responsible for taste discrimination may be located in the central nervous system and most probably occur upstream of the cerebral giant cells. It is also possible to employ the ability of Lymnaea to show taste discrimination following CTA to bring about second-order conditioning. Finally, together with the results showing that extinction of the CTA is difficult, we are lead to the conclusion that the engram of CTA memory is well entrenched in neurons in the central nervous system. This may allow us to more easily employ techniques to uncover the cascade of events that lead to both the establishment and maintenance of long-term memory at the level of single neurons.
|
Acknowledgments |
|---|
|
References |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Benjamin, P. R., Staras, K. and Kemenes, G.
(2000). A systems approach to the cellular analysis of
associative learning in the pond snail Lymnaea. Learn.
Mem. 7,124
-131.
Bouton, M. E. (1993). Context, time, and memory retrieval in the interference paradigms of Pavlovian learning. Psychol. Bull. 114,80 -99.[CrossRef][Medline]
Carew, T. J. and Sahley, C. L. (1986). Invertebrate learning and memory: from behavior to molecules. Annu. Rev. Neurosci. 9,435 -487.[CrossRef][Medline]
Fujie, S., Yamamoto, T., Murakami, J., Hatakeyama, D., Shiga, H., Suzuki, N. and Ito, E. (2005). Nitric oxide synthase and soluble guanylyl cyclase underlying the modulation of electrical oscillations in a central olfactory organ. J. Neurobiol. 62,14 -30.[CrossRef][Medline]
Fulton, D., Kemenes, I., Andrew, R. J. and Benjamin, P. R. (2005). A single time-window for protein synthesis-dependent long-term memory formation after one-trial appetitive conditioning. Eur. J. Neurosci. 21,1347 -1358.[CrossRef][Medline]
Garcia, J., Kimeldorf, D. J. and Koelling, R. A. (1955). Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science 122,157 -158.[Medline]
Garcia, J., Hankins, W. G. and Rusiniak, K. W.
(1974). Behavioral regulation of the melieu interne in man and
rat. Science 185,824
-831.
Garcia, J., Lasiter, P. S., Bermúdez-Rattoni, F. and Deems, D. A. (1985). A general theory of aversion learning. Ann. New York Acad. Sci. 443, 8-21.[Medline]
Haney, J. and Lukowiak, K. (2001). Context
learning and the effect of context on memory retrieval in Lymnaea.Learn. Mem. 8,35
-43.
Hatakeyama, D., Fujito, Y., Sakakibara, M. and Ito, E. (2004a). Expression and distribution of transcription factor CCAAT/enhancer-binding protein in the central nervous system of Lymnaea stagnalis. Cell Tissue Res. 318,631 -641.[CrossRef][Medline]
Hatakeyama, D., Sadamoto, H. and Ito, E. (2004b). Real-time quantitative RT-PCR method for estimation of mRNA level of CCAAT/enhancer binding protein in the central nervous system of Lymnaea stagnalis. Acta Biol. Hung. 55,157 -161.[CrossRef][Medline]
Hatakeyama, D., Inamura, S., Ito, E., Sakakibara, M., Nelson, T. J. and Alkon, D. L. (2004c). Calexcitin-like immunoreactivity in the pond snail Lymnaea stagnalis. Neurosci. Res. Commun. 35,32 -40.[CrossRef]
Hatakeyama, D., Sadamoto, H., Watanabe, T., Wagatsuma, A., Kobayashi, S., Fujito, Y., Yamashita, M., Sakakibara, M., Kemenes, G. and Ito, E. (2006). Requirement of new protein synthesis of a transcription factor for memory consolidation: paradoxical changes in mRNA and protein levels of C/EBP. J. Mol. Biol. 356,569 -577.[CrossRef][Medline]
Ito, E., Kobayashi, S., Kojima, S., Sadamoto, H. and Hatakeyama, D. (1999). Associative learning in the pond snail, Lymnaea stagnalis. Zool. Sci. 16,711 -723.[CrossRef]
Ito, I., Watanabe, S., Kimura, T., Kirino, Y. and Ito, E. (2003a). Negative relationship between odor-induced spike activity and spontaneous oscillations in the primary olfactory system of the terrestrial slug Limax marginatus. Zool. Sci. 20,1327 -1335.[CrossRef][Medline]
Ito, I., Watanabe, S., Kimura, T., Kirino, Y. and Ito, E.
(2003b). Distributions of 
-aminobutyric acid
immunoreactive and acetylcholinesterase-containing cells in the primary
olfactory system in the terrestrial slug Limax marginatus. Zool.
Sci. 20,1337
-1346.[CrossRef][Medline]
Ito, I., Kimura, T., Watanabe, S., Kirino, Y. and Ito, E.
(2004). Modulation of two oscillatory networks in the peripheral
olfactory system by -aminobutyric acid, glutamate, and acetylcholine in
the terrestrial slug Limax marginatus. J. Neurobiol.
59,304
-318.[CrossRef][Medline]
Jones, N. G., Kemenes, I., Kemenes, G. and Benjamin, P. R. (2003). A persistent cellular change in a single modulatory neuron contributes to associative long-term memory. Curr. Biol. 13,1064 -1069.[CrossRef][Medline]
Kawai, R., Sunada, H., Horikoshi, T. and Sakakibara, M. (2004). Conditioned taste aversion with sucrose and tactile stimuli in the pond snail Lymnaea stagnalis. Neurobiol. Learn. Mem. 82,164 -168.[CrossRef][Medline]
Kobayashi, S., Sadamoto, H., Ogawa, H., Kitamura, Y., Oka, K., Tanishita, K. and Ito, E. (2000a). Nitric oxide generation around buccal ganglia accompanying feeding behavior in the pond snail, Lymnaea stagnalis. Neurosci. Res. 38, 27-34.[CrossRef][Medline]
Kobayashi, S., Ogawa, H., Fujito, Y. and Ito, E. (2000b). Nitric oxide suppresses fictive feeding response in Lymnaea stagnalis. Neurosci. Lett. 285,209 -212.[CrossRef][Medline]
Kojima, S., Yamanaka, M., Fujito, Y. and Ito, E. (1996). Differential neuroethological effects of aversive and appetitive reinforcing stimuli on associative learning in Lymnaea stagnalis. Zool. Sci. 13,803 -812.
Kojima, S., Nakamura, H., Nagayama, S., Fujito, Y. and Ito, E. (1997). Enhancement of an inhibitory input to the feeding central pattern generator in Lymnaea stagnalis during conditioned taste-aversion learning. Neurosci. Lett. 230,179 -182.[CrossRef][Medline]
Kojima, S., Kobayashi, S., Yamanaka, M., Sadamoto, H., Nakamura, H., Fujito, Y., Kawai, R., Sakakibara, M. and Ito, E. (1998). Sensory preconditioning for feeding response in the pond snail, Lymnaea stagnalis. Brain Res. 808,113 -115.[CrossRef][Medline]
Kojima, S., Hosono, T., Fujito, Y. and Ito, E. (2001). Optical detection of neuromodulatory effects of conditioned taste aversion in the pond snail Lymnaea stagnalis. J. Neurobiol. 49,118 -128.[CrossRef][Medline]
Lukowiak, K., Sangha, S., McComb, C., Varshney, N., Rosenegger,
D., Sadamoto, H. and Scheibenstock, A. (2003).
Associative learning and memory in Lymnaea stagnalis: how well do
they remember? J. Exp. Biol.
206,2097
-2103.
Mackintosh, N. J. (1974). Extinction. In The Physiology of Animal Learning. pp.405 -483. London: Academic Press.
McComb, C., Rosenegger, D., Varshney, N., Kwok, H. Y. and Lukowiak, K. (2005a). Operant conditioning of an in vitro CNS-pneumostome preparation of Lymnaea. Neurobiol. Learn. Mem. 84,9 -24.[CrossRef][Medline]
McComb, C., Varshney, N. and Lukowiak, K.
(2005b). Juvenile Lymnaea ventilate, learn and remember
differently than do adult Lymnaea. J. Exp. Biol.
208,1459
-1467.
Nakamura, H., Kojima, S., Kobayashi, S., Ito, I., Fujito, Y., Suzuki, H. and Ito, E. (1999a). Physiological characterization of lip and tentacle nerves in Lymnaea stagnalis.Neurosci. Res. 33,291 -298.[CrossRef][Medline]
Nakamura, H., Kobayashi, S., Kojima, S., Urano, A. and Ito, E. (1999b). PKA-dependent regulation of synaptic enhancement between a buccal motor neuron and its regulatory interneuron in Lymnaea stagnalis. Zool. Sci. 16,387 -394.[CrossRef]
Parvez, K., Stewart, O., Sangha, S. and Lukowiak, K.
(2005). Boosting intermediate-term into long-term memory.
J. Exp. Biol. 208,1525
-1536.
Ribeiro, M. J., Serfozo, Z., Papp, A., Kemenes, I., O'Shea, M., Yin, J. C., Benjamin, P. R. and Kemenes, G. (2003). Cyclic AMP response element-binding (CREB)-like proteins in a molluscan brain: cellular localization and learning-induced phosphorylation. Eur. J. Neurosci. 18,1223 -1234.[CrossRef][Medline]
Sadamoto, H., Hatakeyama, D., Kojima, S., Fujito, Y. and Ito, E. (1998). Histochemical study on the relation between NO-generative neurons and central circuitry for feeding in the pond snail, Lymnaea stagnalis. Neurosci. Res. 32, 57-63.[CrossRef][Medline]
Sadamoto, H., Sato, H., Kobayashi, S., Murakami, J., Aonuma, H., Ando, H., Fujito, Y., Hamano, K., Awaji, M., Lukowiak, K. et al. (2004a). CREB in the pond snail Lymnaea stagnalis. Cloning, gene expression and function in identifiable neurons of the central nervous system. J. Neurobiol. 58,455 -466.[CrossRef][Medline]
Sadamoto, H., Azami, S. and Ito, E. (2004b). The expression pattern of CREB genes in the central nervous system of the pond snail Lymnaea stagnalis. Acta Biol. Hung. 55,163 -166.[CrossRef][Medline]
Sahley, C., Rudy, J. W. and Gelperin, A. (1981). An analysis of associative learning in a terrestrial mollusc. I. Higher-order conditioning, blocking and a transient US pre-exposure effect. J. Comp. Physiol. 144, 1-8.[CrossRef]
Sakakibara, M., Aritaka, T., Iizuka, A., Suzuki, H., Horikoshi,
T. and Lukowiak, K. (2005). Electrophysiological
responses to light of neurons in the eye and statocyst of Lymnaea
stagnalis. J. Neurophysiol.
93,493
-507.
Sakura, M., Kabetani, M., Watanabe, S. and Kirino, Y. (2004). Impairment of olfactory discrimination by blockade of nitric oxide activity in the terrestrial slug Limax valentianus.Neurosci. Lett. 370,257 -261.[CrossRef][Medline]
Sangha, S., Scheibenstock, A., Morrow, R. and Lukowiak, K.
(2003). Extinction requires new RNA and protein synthesis and the
soma of the cell right pedal dorsal 1 in Lymnaea stagnalis. J.
Neurosci. 23,9842
-9851.
Sangha, S., Scheibenstock, A., Martens, K., Varshney, N., Cooke, R. and Lukowiak, K. (2005). Impairing forgetting by preventing new learning and memory. Behav. Neurosci. 119,787 -796.[CrossRef][Medline]
Straub, V. A., Styles, B. J., Ireland, J. S., O'Shea, M. and
Benjamin, P. R. (2004). Central localization of plasticity
involved in appetitive conditioning in Lymnaea. Learn.
Mem. 11,787
-793.
Wagatsuma, A., Sugai, R., Chono, K., Azami, S., Hatakeyama, D., Sadamoto, H. and Ito, E. (2004). The early snail acquires the learning. Comparison of scores for conditioned taste aversion between morning and afternoon. Acta Biol. Hung. 55,149 -155.[CrossRef][Medline]
Wagatsuma, A., Sadamoto, H., Kitahashi, T., Lukowiak, K., Urano,
A. and Ito, E. (2005). Determination of the exact copy
numbers of particular mRNAs in a single cell by quantitative real-time RT-PCR.
J. Exp. Biol. 208,2389
-2398.
Yamanaka, M., Sadamoto, H., Hatakeyama, D., Nakamura, H., Kojima, S., Kimura, T., Yamashita, M., Urano, A. and Ito, E. (1999). Developmental changes in conditioned taste aversion in Lymnaea stagnalis. Zool. Sci. 16, 9-16.[Medline]
This article has been cited by other articles:
|
|
 |
|
  M. V. Orr and K. Lukowiak Electrophysiological and Behavioral Evidence Demonstrating That Predator Detection Alters Adaptive Behaviors in the Snail Lymnaea J. Neurosci., March 12, 2008; 28(11): 2726 - 2734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Orr, M. El-Bekai, M. Lui, K. Watson, and K. Lukowiak Predator detection in Lymnaea stagnalis J. Exp. Biol., December 1, 2007; 210(23): 4150 - 4158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sugai, S. Azami, H. Shiga, T. Watanabe, H. Sadamoto, S. Kobayashi, D. Hatakeyama, Y. Fujito, K. Lukowiak, and E. Ito One-trial conditioned taste aversion in Lymnaea: good and poor performers in long-term memory acquisition J. Exp. Biol., April 1, 2007; 210(7): 1225 - 1237. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
