Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Amygdala-dependent Mechanisms Underlying Memory Retrieval of Conditioned Taste Aversion
1 Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University, Fukushima 960-1295, Japan and 2 Department of Behavioral Physiology, Graduate School of Human Sciences, Osaka University, Osaka, Japan
Correspondence to be sent to: Yasunobu Yasoshima, e-mail: yasosima{at}fmu.ac.jp
Key words: AMPA receptor, desipramine, midazolam, taste memory trace
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Introduction |
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 Top Introduction Involvement of the amygdala...Transmitter systems in the...ConclusionAcknowledgementsReferences |
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Conditioned taste aversion (CTA) is an associative learning phenomenon in which ingestion of a novel tasting food or fluid (conditioned stimulus, CS) is paired with visceral malaise (unconditioned stimulus, US) (Yamamoto et al., 1994
). Conditioned animals avoid
ingesting the tastant previously associated with the condition of sickness. Since CTA is
established by a single pairing of the CS and US, it is easy to distinguish different
memory-related phases: acquisition, consolidation, reconsolidation and retrieval. This
unique property of CTA is useful in identification and manipulation of the underlying
physiological and molecular mechanisms responsible for each memory phase.
There is a large amount of evidence that the amygdala plays an important role in the
acquisition and retention of CTA (see, for example,
Miranda et al., 2003). The
amygdala receives a variety of sensory inputs, including gustatory and visceral
information. It also has many kinds of transmitter systems, such as glutamatergic,
noradrenergic (NAergic), dopaminergic and other innervations, and contains inhibitory
interneurons containing 
-aminobutyric acid (GABA) as a neurotransmitter. Although
there have been several reports about the roles of amygdalar transmitter systems in CTA
acquisition, the functioning of the transmitter systems responsible for the retrieval has
not been completely elucidated. In this paper, we summarize our findings regarding
amygdalar mechanisms for retrieval of CTA memory.
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Involvement of the amygdala in memory retrieval |
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TopIntroductionInvolvement of the amygdala...Transmitter systems in the...ConclusionAcknowledgementsReferences |
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There are several critical brain regions that affect CTA formation: the parabrachial nucleus, the parvicellular region of the ventroposteromedial nucleus of the thalamus (VPMpc), the basolateral nucleus of the amygdala (BLA) and the cortical gustatory area (CGA) in the insular cortex (Yamamoto et al., 1994
). Lesion of one of these structures before conditioning
impedes the acquisition of CTA (Yamamoto et
al., 1994). However, the brain sites responsible for the retention of
CTA remain unclear. Lesions in the CGA, hippocampus (HIP) or the central nucleus of the
amygdala (CeA) that are formed after conditioning do not affect retention and retrieval
of CTA in a first retention test; instead, lesion of the CGA or HIP accelerated
extinction. On the other hand, lesion of the VPMpc or BLA formed after conditioning
impaired retention and retrieval. Hence, these results suggest that the BLA, not the CGA,
is involved in retrieval of CTA memory (Yamamoto,
1994).
In an electrophysiological study in freely behaving animals, the taste responses to
the CS in BLA neurons during retrieval were enhanced after conditioning. In contrast, the
activity of some CeA neurons was suppressed during CS presentation (Yasoshima et al., 1995). These results are
consistent with the notion that the BLA is involved in the retrieval process.
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Transmitter systems in the amygdala |
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TopIntroductionInvolvement of the amygdala...Transmitter systems in the...ConclusionAcknowledgementsReferences |
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Glutamatergic transmission
When an AMPA receptor antagonist, CNQX, was infused into the BLA in conditioned rats
before the retention test, the rats drank a larger amount of the CS, compared to rats
infused with vehicle solution. However, the same rats infused with CNQX showed a strong
aversion to the CS in a subsequent test without drug infusion. The reversible and
transient memory deficit caused by intra-BLA CNQX infusion was also induced in the
stronger CTA formation developed using the twice conditioning procedure. On the contrary,
infusions of an NMDA receptor antagonist or a metabotropic receptor antagonist, MCPG,
before the retention test did not cause memory disruption (Figure
1). These results suggest that the
retrieval process is mediated by the activation of AMPA receptors, but not NMDA or
metabotropic receptors, in the BLA (Yasoshima
et al., 2000). The results also suggest that blocking of AMPA
receptors in the BLA does not modify the CTA memory trace, while blocking of NMDA
receptors in the BLA during reactivation of CTA memory significantly attenuates retention
of CTA memory (Figure
1). This latter result suggests that
NMDA receptors in the BLA are involved in the reconsolidation of CTA memory.
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NAergic transmission
Recent findings indicate that NAergic function is involved in CTA memory formation.
Although there have been many studies about the involvement of NAergic transmission in
the amygdala, the contribution of the NAergic system during each memory phase has not
been clearly elucidated. Mice heterozygous for a mutation in the tyrosine hydroxylase
gene showed rapid extinction of CTA (Kobayashi
et al., 2000). When the NAergic function in the mutants was
upregulated by an i.p. injection of desipramine, an uptake inhibitor of NA, after
conditioning, memory deficit was restored. These results suggest that the NAergic system
plays an important role in retention of CTA memory.
GABA/benzodiazepine transmission
CTA retrieval was disrupted by an i.p. injection of midazolam (MDZ, 1.5 mg/kg), a benzodiazepine (BDZ) agonist, in conditioned animals. The disruption induced by MDZ was reversible and transient, because a strong aversion to the CS was apparent in a subsequent test in the same animals. When MDZ was infused into the rat BLA, the latency for rejection of intraorally infused CS was longer than that in PBS-infused rats (Yasoshima et al., unpublished data). These results suggest that activation of GABAA/BDZ receptors in the BLA reversibly impairs retrieval of CTA memory, although the transient activation of the inhibitory system in the BLA does not destroy the CTA memory trace.
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Conclusion |
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TopIntroductionInvolvement of the amygdala...Transmitter systems in the...ConclusionAcknowledgementsReferences |
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Retrieval of the CTA memory and motor commands elicited by CTA memory reactivation is mediated by activation of AMPA receptors and inhibited by GABAA/BDZ receptors in the BLA. The NAergic function in the amygdala facilitates memory formation.
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Acknowledgements |
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TopIntroductionInvolvement of the amygdala...Transmitter systems in the...ConclusionAcknowledgementsReferences |
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Parts of the studies in this article were supported by Grants-in-Aid for 21st Century COE and Scientific Research from the Ministry of Education, Science, Culture and Sports of Japan to Y.Y. (16700289) and T.Y. (1430593 and 16659510).
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Yamamoto, T. (1994) A neural model for taste aversion learning. In Kurihara, K., Suzuki, N. and Ogawa, H. (eds), Olfaction and Taste XI. Springer, Tokyo, pp. 471–474.
Yamamoto, T., Shimura, T., Sako, N., Yasoshima, Y. and Sakai, N. (1994) Neural substrates for conditioned taste aversion in the rat. Behav. Brain Res., 15, 123–137.
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