Luis Núñez-Jaramillo

Cholinergic dependence of taste memory formation: Evidence of two distinct processes

Learning the aversive or positive consequences associated with novel taste solutions has a strong significance for an animals survival. A lack of recognition of a tastes consequences could prevent ingestion of potential edibles or encounter death. We used conditioned taste aversion (CTA) and attenuation of neophobia (AN) to study aversive and safe taste memory formation. To determine if muscarinic receptors in the insular cortex participate differentially in both tasks, we infused the muscarinic antagonists scopolamine at distinct times before or after the presentation of a strong concentration of saccharin, followed by either an i.p. injection of a malaise-inducing agent or no injection. Our results showed that blockade of muscarinic receptors before taste presentation disrupts both learning tasks. However, the same treatment after the taste prevents AN but not CTA. These results clearly demonstrate that cortical cholinergic activity participates in the acquisition of both safe and aversive memory formation, and that cortical muscarinic receptors seem to be necessary for safe but not for aversive taste memory consolidation. These results suggest that the taste memory trace is processed in the insular cortex simultaneously by at least two independent mechanisms, and that their interaction would determine the degree of aversion or preference learned to a novel taste.

Taste memory formation: Latest advances and challenges

Taste memory has been a useful model for studying memory formation; using different approaches ranging from lesion studies, analysis of receptor and neurotransmitter activity, and measurement of intracellular signaling mechanisms or gene expression, it has been possible to describe processes which may be involved in several types of memory. Taste memory includes the recognition of a taste as well as its characteristics related to the hedonic value, degree of familiarity, and the nutritive or toxic properties associated with that taste. In terms of evolutionary adaptation, taste memory is necessary for the proper identification of available nutritive foods and, of course, is essential to avoid deadly toxins. This review summarizes the current knowledge of taste memory, describing the evidence obtained using non-associative and associative taste learning models by manipulating the different structures involved in the formation and expression of taste memory. Pharmacological, biochemical, and molecular data are shown for each structure and subsequently current theories are presented about possible inter-structural interactions taking part in taste memory formation. Finally, we describe how the study of taste memory can reveal basic mechanisms of learning, raising issues that might apply to learning processes in general.

Taste novelty induces intracellular redistribution of NR2A and NR2B subunits of NMDA receptor in the insular cortex.

Taste recognition memory is a process by which animals associate a taste previously experienced with its gastric consequences. Novel taste presentation induces in the insular cortex biochemical modifications that decrease after the taste becomes familiar. Here we show that, in this cortex, consumption of a novel taste produces an increase of the NR2A and NR2B subunits of the NMDA receptor in the detergent resistant membrane (DRM) fraction. This increase did not occur in the adjacent parietal cortex, was not due to a change in the total amount of protein, and is related with the novelty of the stimulus since it was reduced after the taste became familiar. Furthermore, NR2A and NR2B subunits increase in the DRM was blocked by the injection of a muscarinic acetylcholine receptor antagonist. These results suggest that modulation of NMDA receptors in the insular cortex through the increase of its NR2A and NR2B subunits in the DRM is involved in the taste memory formation via a cholinergic process.

PKC blockade differentially affects aversive but not appetitive gustatory memories

After consumption of a new taste, there are mainly two possible outcomes for the establishment of a taste memory, either it will be aversive or safe depending on the consequences of taste consumption. It has been proposed that both types of learning share a common initial taste memory trace, which will lead to two different memory traces, safe or aversive. To study the role of PKC activity in aversive or safe taste memory formation, we administered chelerythrine, a PKC inhibitor, into the insular cortex or parietal cortex 20 min before conditioned taste aversion or attenuation of neophobia training. The results suggest that PKC activity is needed in the insular cortex for the establishment of aversive taste memory, but not for safe taste memory.

Differential effects of β-adrenergic receptor blockade in the medial prefrontal cortex during aversive and incidental taste memory formation.

The medial prefrontal cortex (mPFC) is a brain area crucial for memory, attention, and decision making. Specifically, the noradrenergic system in this cortex is involved in aversive learning, as well as in the retrieval of these memories. Some evidence suggests that this area has an important role during taste memory, particularly during conditioned taste aversion (CTA), a model of aversive memory. Despite some previous evidence, there is scarce information about the role of adrenergic receptors in the mPFC during formation of aversive taste memory and appetitive/incidental taste memory. The goal of this research was to evaluate the role of mPFC beta-adrenergic receptors during CTA acquisition/consolidation or CTA retrieval, as well as during incidental taste memory formation using the model of latent inhibition of CTA. The results showed that infusions in the mPFC of the beta-adrenergic antagonist propranolol before CTA acquisition impaired both short- and long-term aversive taste memory formation, and also that propranolol infusions before the memory test impaired CTA retrieval. However, propranolol infusions before pre-exposure to the taste during the latent inhibition procedure had no effect on incidental taste memory acquisition or consolidation. These data indicate that beta-adrenergic receptors in the mPFC have different functions during taste memory formation: they have an important role during aversive taste association as well as during aversive retrieval but not during incidental taste memory formation.

Activation of nucleus accumbens NMDA receptors differentially affects appetitive or aversive taste learning and memory

Taste memory depends on motivational and post-ingestional consequences; thus, it can be aversive (e.g., conditioned taste aversion, CTA) if a novel, palatable taste is paired with visceral malaise, or it can be appetitive if no intoxication appears after novel taste consumption, and a taste preference is developed.The nucleus accumbens (NAc) plays a role in hedonic reactivity to taste stimuli, and recent findings suggest that reward and aversion are differentially encoded by the activity of NAc neurons. The present study examined whether the requirement for N-methyl-D-aspartate (NMDA) receptors in the NAc core during rewarding appetitive taste learning differs from that during aversive taste conditioning, as well as during retrieval of appetitive vs. aversive taste memory, using the taste preference or CTA model, respectively. Bilateral infusions of NMDA (1 μg/μl, 0.5 μl) into the NAc core were performed before acquisition or before retrieval of taste preference or CTA. Activation of NMDA receptors before taste preference training or CTA acquisition did not alter memory formation. Furthermore, NMDA injections before aversive taste retrieval had no effect on taste memory; however, 24 h later, CTA extinction was significantly delayed. Also, NMDA injections, made before familiar appetitive memory retrieval, interrupted the development of taste preference and produced a preference delay 24 h later. These results suggest that memory formation for a novel taste produces neurochemical changes in the NAc core that have differential requirements for NMDA receptors during retrieval of appetitive or aversive memory.

Blockade of nucleus basalis magnocellularis or activation of insular cortex histamine receptors disrupts formation but not retrieval of aversive taste memory

Recent research, using several experimental models, demonstrated that the histaminergic system is clearly involved in memory formation. This evidence suggested that during different associative learning tasks, histamine receptor subtypes have opposite functions, related to the regulation of cortical cholinergic activity. Given that cortical cholinergic activity and nucleus basalis magnocellularis (NBM) integrity are needed during taste memory formation, the aim of this study was to determine the role of histamine receptors during conditioned taste aversion (CTA). We evaluated the effects of bilateral infusions of 0.5 microl of pyrilamine (100 mM), an H(1) receptor antagonist, into the NBM, or of R-alpha-methylhistamine (RAMH) (10 mM), an H(3) receptor agonist, into the insular cortex of male Sprague-Dawley rats 20 min before acquisition and/or retrieval of conditioned taste aversion. The results showed that blockade of H(1) receptors in NBM or activation of H(3) receptors in the insular cortex impairs formation but not retrieval of aversive taste memory. These results demonstrated differential roles for histamine receptors in two important areas for taste memory formation and suggest that these effects could be related with the cortical cholinergic activity modulation during CTA acquisition.

The role of dopamine D2 receptors in the nucleus accumbens during taste-aversive learning and memory extinction after long-term sugar consumption

The nucleus accumbens (NAcc) is a forebrain region that may significantly contribute to the integration of taste and visceral signals during food consumption. Changes in dopamine release in the NAcc have been observed during consumption of a sweet taste and during compulsive consumption of dietary sugars, suggesting that NAcc dopaminergic transmission is strongly correlated with taste familiarity and the hedonic value content. NAcc core and shell nuclei are differentially involved during and after sugar exposure and, particularly, previous evidence suggests that dopamine D2 receptors could be related with the strength of the latent inhibition (LI) of conditioned taste aversion (CTA), which depends on the length of the taste stimulus pre-exposure. Thus, the objective of this work was to evaluate, after long-term exposure to sugar, the function of dopaminergic D2 receptors in the NAcc core during taste memory retrieval preference test, and during CTA. Adult rats were exposed during 14days to 10% sugar solution as a single liquid ad libitum. NAcc core bilateral injections of D2 dopamine receptor antagonist, haloperidol (1μg/μL), were made before third preference test and CTA acquisition. We found that sugar was similarly preferred after 3 acute presentations or 14days of continued sugar consumption and that haloperidol did not disrupt this appetitive memory retrieval. Nevertheless, D2 receptors antagonism differentially affects aversive memory formation after acute or long-term sugar consumption. These results demonstrate that NAcc dopamine D2 receptors have a differential function during CTA depending on the degree of sugar familiarity.

β-Adrenergic receptors in the insular cortex are differentially involved in aversive vs. incidental context memory formation

The goal of this research was to determine the effects of β-adrenergic antagonism in the IC before or after inhibitory avoidance (IA) training or context pre-exposure in a latent inhibition protocol. Pretraining intra-IC infusion of the β-adrenergic antagonist propranolol disrupted subsequent IA retention and impaired latent inhibition of IA, but had no effect on formation of memory for an inert context (termed incidental memory). These results indicate that IC β-adrenergic receptors are necessary for memory acquisition of an aversive, but not an inconsequential, context. Nevertheless, subsequent association of a familiar and hitherto inconsequential context with an unconditioned stimulus (US) does require activation of these receptors during its initial acquisition.

Effects of glutamate and its metabotropic receptors class 1 antagonist in appetitive taste memory formation

Cortical glutamatergic activity is known to be important for memory formation in different learning tasks. For example, glutamate activity in the insular cortex plays an important role in aversive taste memory formation by signaling the unconditioned stimulus. However, the role of glutamate in the insular cortex in appetitive taste learning has remained poorly studied. Therefore, we considered the function of glutamate in attenuation of neophobia, a model of appetitive taste recognition memory. For this purpose, we performed infusions of vehicle, glutamate, a specific mGluR1 antagonist (AIDA) or a combination of glutamate and AIDA at 0 or 30 min, and glutamate or vehicle at 60 min after novel saccharin consumption. Glutamate infusion impaired appetitive taste recognition memory when infused at 0 or 30 min, whereas, AIDA infusions produced enhanced appetitive memory at the same infusion times. Furthermore, when glutamate and AIDA were infused together no effect on attenuation of neophobia was observed. As opposed to shorter infusion times, the administration of glutamate 60 min after the presentation of the saccharin consumption was ineffective in the impairment of the appetitive taste memory. These results are discussed in view of the effect of glutamate and its mGluR1 during the appetitive taste recognition memory formation in the insular cortex.