Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Neurobiology of Taste-recognition Memory Formation
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-253, 04510 México D.F., México
Correspondence to be sent to: Federico Bermudez-Rattoni, e-mail: fbermude{at}ifc.unam.mx
Key words: conditioning, insular cortex, learning, memory, recognition memory, taste
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Introduction |
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 Top Introduction CS signalsCS-US associationCortical (CS)-amygdala (US)...AcknowledgementsReferences |
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Recognition memory is the ability to assert the familiarity of things previously encountered. In the case of food, when an animal encounters a new taste, it hesitates to eat it, showing a reduced consumption—a neophobic response. However, when the new taste has no negative consequences, it becomes recognized as a safe signal, leading to an increase in its consumption (attenuation of neophobia). But if the new taste is associated with malaise, animals develop a long-lasting aversion to that taste—the taste cue becomes an aversive signal—rejecting it the next time they encounter it, being the taste the conditioned stimulus (CS) and the malaise inducing agent the unconditioned stimulus (US). This form of recognition memory is referred to as conditioned taste aversion (CTA) (Bermudez-Rattoni, 2004
).
Both aversive and safe taste memories depend on the neural representation of the
taste that probably remains temporarily stored in several brain regions in parallel where
it might be processed in either direction (safe or aversive taste memory) (Bermudez-Rattoni, 2004). This neural
representation has been called the taste memory trace (TMT) (Bermudez-Rattoni, 2004). However, it still remains to be
demonstrated whether the TMT has two independent components (aversive and safe), or if
there is only one TMT, which could be converted into an aversive TMT when it is
associated with visceral malaise.
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CS signals |
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TopIntroductionCS signalsCS-US associationCortical (CS)-amygdala (US)...AcknowledgementsReferences |
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Taste information reaches forebrain structures such as the amygdala and the insular cortex (IC) and permanent or reversible lesions of these two structures impair taste memory formation (see Bermudez-Rattoni, 2004
). Inside these
structures information is processed by different mechanisms, among which the cholinergic
system has been widely studied. It has been demonstrated by using microdialysis in freely
moving rats a marked increase in the release of acetylcholine (ACh) in the IC induced by
the first presentation of a new taste, compared to the release elicited by the
presentation of a familiar taste like water (Miranda et al., 2000). This is highly significant
because taste novelty is a determinant factor in the establishment of gustatory memory
(Miranda et al., 2000). After
several presentations of a given taste, there was a significant decrease of ACh release
as the taste became familiar (Miranda et
al., 2000). These data point to an inverse relationship between taste
familiarity and cortical ACh release. Since no gastric malaise was induced after
saccharin presentation, these results suggest a participation of the muscarinic ACh
receptors in the insular cortex when a novel taste becomes a safe familiar one. In this
regard, several experiments have shown that a 2–4 h continuous period in which
noxious consequences of food ingestion are absent is required to classify a gustatory
stimulus as safe or neutral (Bermudez-Rattoni,
2004).
After the injection of scopolamine, an antagonist of muscarinic ACh receptors, in the
IC before the first presentation of a taste that produces a robust neophobic response,
consumption remained unaltered in the acquisition session. However, 1 day later, when
saccharin was presented again, the animals that received scopolamine showed a strong
neophobic response, as if it were the first time that they experienced this taste,
indicating that scopolamine prevented a new taste from becoming familiar. Importantly,
the attenuation of neophobia was impaired only if scopolamine was administered before or
up to 2 h after the new taste (Gutierrez et
al., 2003).
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CS–US association |
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TopIntroductionCS signalsCS-US associationCortical (CS)-amygdala (US)...AcknowledgementsReferences |
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Synergistic interactions between cholinergic and glutamatergic systems seems to be critical for memory formation (for a review, see Woolf, 1996
) and glutamate has been
implicated in the consolidation of several memory tasks, such as inhibitory avoidance,
the Morris water maze and CTA (Kim and McGaugh,
1992;
Ferreira et al., 2002).
Recently, it has been demonstrated by in vivo microdialysis that injection
of LiCl, but not the presentation of saccharin, elicited a marked increase in glutamate
release in the amygdala and a modest but significant release in the IC (Miranda et al., 2002). In addition,
while the injection of a low concentration of LiCl after saccharin presentation induces a
weak CTA, a reliable and robust aversive CTA can be elicited with this low concentration
of LiCl when accompanied by microinjections of glutamate directly into the amygdala
(Miranda et al., 2002).
Furthermore, it has been shown that the application of AMPA, NMDA or metabotropic
glutamate receptor antagonists into the amygdala after the new taste or before the LiCl
is presented impaired the formation of long-term taste aversion memory (Yasoshima et al., 2000). It was
concluded that glutamatergic transmission is involved in the formation of the long-term
gustatory memory that is associated with the altered hedonic change from safe to aversive
TMT (Yasoshima et al.,
2000).
Similar results were found for NMDA receptors in the IC. Thus, NMDA receptor
antagonists when applied in the IC either before or after the acquisition trial disrupted
CTA (Ferreira et al., 2002).
For comparison, intracortical microinjection of the muscarinic antagonist scopolamine
applied before the presentation of the new taste, but not afterwards, abolished aversive
taste memory formation (Ferreira et al.,
2002). These results indicate that glutamate might convey the visceral input
that eventually converges with the CS during the association and consolidation phases of
aversive TMT formation. These data confirm that cholinergic activity is involved in the
TMT formation, whereas glutamatergic activity participates in promoting the formation of
an aversive TMT, probably suppressing the formation of a safe TMT (see Figure
1).
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Cortical (CS)–amygdala (US) interactions |
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TopIntroductionCS signalsCS-US associationCortical (CS)-amygdala (US)...AcknowledgementsReferences |
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Activity-dependent changes in the efficacy of synaptic transmission are considered to be of fundamental importance for memory formation. In vivo tetanic stimulation of the basolateral nucleus of amygdala induces long-term potentiation (LTP) in the insular cortex of adult rats, significantly increasing the synaptic responses to low frequency stimulation during a period of at least 1 h after stimulation and its induction in this projection before CTA training enhances the retention of this task (Escobar and Bermudez-Rattoni, 2000
). These
results suggest that the potentiation of the amygdala-cortical projection is a possible
mechanism for memory-related functions performed by the insular cortex. Inracortical
administration of NMDA receptor-competitive antagonist
(3-2carboxipiperazin-4-yl-propyl-1-phosphonic acid, CPP) disrupts the acquisition of CTA,
as well as the BLA–insular cortex–LTP induction in vivo (Escobar et al., 2002). These results
point to a cortical facilitation induced by amygdala stimulation that seems to be
regulated by glutamate through its NMDA receptors in the IC.
As noted before, injection of a low dose of lithium chloride (25 mg/kg, i.p.) 30
min after novel taste consumption (saccharin 0.1%) induces a weak CTA, which can
be improved by injection of glutamate into the amygdala (Miranda et al., 2002). In an unpublished work, we
showed that cortical microinjections of a NMDA antagonist reverse the memory-enhancing
effect of BLA glutamate injection. This further supports an important amygdalo-cortical
interaction during CTA memory formation and a crucial role for glutamatergic system in
the IC for CTA consolidation.
As shown in Figure
1, consumption of a new taste leads to
sustained tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the IC
(Rosenblum et al., 1997) and
application of tyrosine kinase inhibitors block aversive memories, including taste
aversion (Yasoshima and Yamamoto,
1997). This phosphorylation is dependent on the muscarinic receptors
activation by the taste and can be reproduced by the administration of carbachol in the
IC (Rosenblum et al., 1995).
Together, these results indicate that there is an inverse relationship between the
familiarity of the taste and the phosphorylation of the NR2B subunits. Although the role
of this phosphorylation remains to be established, it might facilitate the formation of
the malaise-induced aversion (Miranda et
al., 2002;
Gutierrez et al., 2003),
since this phosphorylation potentiates the NMDA channel activity and has also been
related with the activation of intracellular signaling (Mizuno et al., 2003). Thus, after phosphorylation,
the NMDA receptor in the IC might generate an increased response to the stimulation
coming from the amygdala and carrying the US information and transforming the safe in
aversive TMT.
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Acknowledgements |
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TopIntroductionCS signalsCS-US associationCortical (CS)-amygdala (US)...AcknowledgementsReferences |
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This work was supported by grants CONACyT and DGAPA-UNAM.
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TopIntroductionCS signalsCS-US associationCortical (CS)-amygdala (US)...AcknowledgementsReferences |
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