Critical role of amygdala in flavor but not taste preference learning in rats

The role of the amygdala (AMY) in learning to associate complex flavor (taste + odor cues) with the oral and post-oral properties of nutrients was examined. Rats with excitotoxic lesions of the basolateral AMY learned to prefer flavors paired with intragastric (IG) infusions of maltodextrin or corn oil (Experiment 1), although the preference was slightly attenuated. However, rats with large AMY lesions failed to develop a preference for flavors paired with IG infusions of the same nutrients (Experiments 2 and 4) but were able to learn a preference for a taste mixture paired with IG maltodextrin infusions (Experiment 3). The rats with large AMY lesions also did not acquire a preference for a flavor cue paired with the sweet taste of fructose (Experiment 5). Collectively, these data provide evidence that AMY is essential for flavor- but not taste-nutrient preference learning.     

Basolateral amygdala lesions disrupt latent inhibitionin rats

Latent inhibition (LI) refers to the retardation of acquisition of conditioned responding produced by repeated non-reinforced preexposure to the conditioned stimulus (CS) prior to its pairing with the unconditioned stimulus (US) during conditioning. LI has recently been shown to depend upon the integrity of temporal lobe structures, including regions of the hippocampal formation such as the entorhinal cortex. The present study investigated the effects of excitotoxic lesions of another temporal lobe structure, the basolateral nucleus of the amygdala (BLA), on LI. LI was studied in a within-subjects appetitive conditioning preparation in which an auditory CS was paired with food US. In this procedure, preexposure to the CS results in slower acquisition of magazine approach behaviour. Lesions of the BLA reduced the effect of preexposure, disrupting LI. This result suggests that the BLA can play a crucial role in LI. The possible involvement of interactions between BLA and entorhinal cortex in LI is discussed.     

Dissociable effects of disconnecting amygdala central nucleus from the ventral tegmental area or substantia nigra on learned orienting and incentive motivation

Recent evidence suggests that the amygdala central nucleus (CeA) and midbrain-striatal dopamine systems are critically involved in the alteration of attentional and emotional processing of initially neutral stimuli by associative learning. In rats, the acquisition of learned orienting responses (ORs) to visual cues paired with food is impaired by lesions of the CeA, and by lesions that disconnect CeA from the dorsolateral striatum (DLS), a region traditionally implicated in elevated responsiveness to sensory stimuli. Similarly, the acquisition of emotional significance to cues paired with food also depends on the function of CeA and of the ventral striatal nucleus accumbens (ACB), a region often considered crucial to acquired reward and motivation. For example, the ability of a cue previously paired with food to increase the rate of food-reinforced instrumental responding (Pavlovian-instrumental transfer, PIT) is eliminated by lesions of the CeA or the accumbens core. In this experiment, we found that lesions that functionally disconnected CeA from the substantia nigra pars compacta (SNc) impaired the acquisition of conditioned orienting to auditory cues paired with food, but had no effect on their ability to enhance instrumental responding, relative to the effects of unilateral lesions of that region. By contrast, lesions that disconnected CeA from the ventral tegmental area (VTA) had no effect on the acquisition of conditioned orienting, but facilitated Pavlovian-instrumental transfer relative to unilateral midbrain lesions, rescuing that function to sham-lesion control levels. Otherwise, unilateral lesions of either midbrain region impaired transfer. Implications of these results for circuit models of amygdalo-striatal interactions in associative learning are discussed.     

Emotion and motivation: the role of the amygdala,ventral striatum,and prefrontal cortex

Emotions are multifaceted, but a key aspect of emotion involves the assessment of the value of environmental stimuli. This article reviews the many psychological representations, including representations of stimulus value, which are formed in the brain during Pavlovian and instrumental conditioning tasks. These representations may be related directly to the functions of cortical and subcortical neural structures. The basolateral amygdala (BLA) appears to be required for a Pavlovian conditioned stimulus (CS) to gain access to the current value of the specific unconditioned stimulus (US) that it predicts, while the central nucleus of the amygdala acts as a controller of brainstem arousal and response systems, and subserves some forms of stimulus-response Pavlovian conditioning. The nucleus accumbens, which appears not to be required for knowledge of the contingency between instrumental actions and their outcomes, nevertheless influences instrumental behaviour strongly by allowing Pavlovian CSs to affect the level of instrumental responding (Pavlovian-instrumental transfer), and is required for the normal ability of animals to choose rewards that are delayed. The prelimbic cortex is required for the detection of instrumental action-outcome contingencies, while insular cortex may allow rats to retrieve the values of specific foods via their sensory properties. The orbitofrontal cortex, like the BLA, may represent aspects of reinforcer value that govern instrumental choice behaviour. Finally, the anterior cingulate cortex, implicated in human disorders of emotion and attention, may have multiple roles in responding to the emotional significance of stimuli and to errors in performance, preventing responding to inappropriate stimuli.     

Insular cortex lesions fail to block flavor and taste preference learning in rats

The role of the insular cortex (IC) in learning to associate orosensory cues with the oral and post-oral properties of carbohydrate was examined. Rats with either small (gustatory region) or large (gustatory and visceral regions) ibotenic acid lesions of the IC learned to prefer flavors (Experiments 1 and 3) and taste mixtures (Experiments 2 and 4) paired with intragastric infusions of maltodextrin. The rats with large IC lesions also learned a preference for a flavor cue paired with the sweet taste of fructose (Experiment 5). In fact, they showed enhanced conditioning and retarded extinction compared with controls. Collectively, these data provided no evidence that IC is essential for flavor preference learning based on associations between the orosensory cues and the oral and post-oral reinforcing properties of nutrients.     

Preference formation and working memory in Parkinson's disease and normal ageing.

Recent studies in rats have suggested that the amygdala and the dorsal striatum may be differentially involved in the formation of stimulus-reward associations and stimulus-response associations, respectively. In a recent study in humans, conditioned preference learning deficits were observed in a group of patients with damage to the amygdala formation. In this study, patients with Parkinson's disease, which is known to involve pathology of the dorsal striatum, were tested on the same conditioned preference task, together with a group of patients with circumscribed lesions of the frontal lobe. Unlike patients with frontal lobe damage, patients with Parkinson's disease did not exhibit conditioned preferences. However, in this respect their behaviour was indistinguishable from that of age-matched (older) control subjects. In keeping with previous literature, working memory deficits were observed in both patients with Parkinson's disease and patients with frontal-lobe lesions. Compared to young control subjects, a strong increase in preference for familiar, versus novel, items was observed in both patients with Parkinson's disease and in older control subjects. Such a familiarity effect appears to overshadow the conditioning manipulation employed in this task and, therefore, preclude the expression of conditioned preferences in older subjects. These results suggest that there is a developmental progression in the degree to which different mechanisms of 'learning to like' are important over the life span.     

Orbitofrontal cortex and representation of incentive value in associative learning.

Clinical evidence indicates that damage to ventromedial prefrontal cortex disrupts goal-directed actions that are guided by motivational and emotional factors. As a consequence, patients with such damage characteristically engage in maladaptive behaviors. Other research has shown that neurons in the corresponding orbital region of prefrontal cortex in laboratory animals encode information regarding the incentive properties of goals or expected events. The present study investigates the effect of neurotoxic orbitofrontal cortex (OFC) lesions in the rat on responses that are normally influenced by associations between a conditioned stimulus (CS) and the incentive value of reinforcement. Rats were first trained to associate a visual CS with delivery of food pellets to a food cup. As a consequence of learning, rats approached the food cup during the CS in anticipation of reinforcement. In a second training phase, injection of LiCl followed consumption of the food unconditioned stimulus (US) in the home cage, a procedure used to alter the incentive value of the US. Subsequently, rats were returned to the conditioning chamber, and their responding to the CS in the absence of the food US was tested. Lesions of OFC did not affect either the initial acquisition of a conditioned response to the light CS in the first training phase or taste aversion learning in the second training phase. In the test for devaluation, however, OFC rats exhibited no change in conditioned responding to the visual CS. This outcome contrasts with the behavior of control rats; after devaluation of the US a significant decrease occurred in approach to the food cup during presentation of the CS. The results reveal an inability of a cue to access representational information about the incentive value of associated reinforcement after OFC damage.     

The role of the dorsomedial striatum in instrumental conditioning

Considerable evidence suggests that, in instrumental conditioning, rats learn the relationship between actions and their specific consequences or outcomes. The present study examined the role of the dorsomedial striatum (DMS) in this type of learning after excitotoxic lesions and reversible, muscimol-induced inactivation. In three experiments, rats were first trained to press two levers for distinct outcomes, and then tested after training using a variety of behavioural assays that have been established to detect action-outcome learning. In Experiment 1, pre-training lesions of the posterior DMS abolished the sensitivity of rats' instrumental performance to both outcome devaluation and contingency degradation when tested in extinction, whereas lesions of the anterior DMS had no effect. In Experiment 2, both pre-training and post-training lesions of the posterior DMS were equally effective in reducing the sensitivity of performance both to devaluation and degradation treatments. In Experiment 3, the infusion of muscimol into the posterior DMS selectively abolished sensitivity of performance to devaluation and contingency degradation without impairing the ability of rats to discriminate either the instrumental actions performed or the identity of the earned outcomes. Taken together, these results suggest that the posterior region of the DMS is a crucial neural substrate for the acquisition and expression of action-outcome associations in instrumental conditioning.     

Dopamine D1-like receptor antagonism in amygdala impairs the acquisition of glucose-conditioned flavor preference in rats

This study examined the role of dopamine within the amygdala (AMY) in flavor preference learning induced by post-oral glucose. In Experiment 1, rats were trained with a flavor [conditioned stimulus (CS+)] paired with intragastric (IG) infusions of 8% glucose and a different flavor (CS−) paired with IG water infusions. The CS+ preference was evaluated in two-bottle tests following bilateral injection of the dopamine D1-like receptor antagonist, SCH23390 (SCH), into the AMY at total doses of 0, 12, 24 and 48 nmol. SCH produced dose-dependent reductions in CS+ intake but did not block the CS+ preference except at the two highest doses, which also greatly suppressed the CS intakes. In Experiment 2, new rats were injected daily in the AMY with either saline or SCH (12 nmol), prior to training sessions with CS+/IG glucose and CS−/IG water. In the two-bottle tests, SCH rats, unlike the control rats, failed to prefer the CS+ (55 vs. 81%). In Experiments 3 and 4, new rats were trained as in Experiment 2, except that brain injections were in the basolateral and central nuclei of the AMY, respectively. SCH rats learned to prefer the CS+ to the CS−, although their preference was weaker than that displayed by the control rats (Experiment 3: 59 vs. 80%; Experiment 4: 73 vs. 88%). These results show an essential role for D1-like receptor activation in the AMY in the acquisition of flavor preference learning induced by the post-oral reinforcing properties of glucose. A distributed network mediating flavor–nutrient incentive learning is discussed.     

Double dissociation of the effects of lesions of basolateral and central amygdala on conditioned stimulus-potentiated feeding and Pavlovian-instrumental transfer

Pavlovian conditioned stimuli (CSs) for food can enhance both the performance of instrumental responses that earn food (Pavlovian-instrumental transfer; PIT) and the consumption of food itself (CS-potentiated feeding). After a single phase of Pavlovian training, each rat was tested in both PIT and potentiated feeding tasks. Rats with lesions of the central nucleus of the amygdala failed to exhibit PIT but showed normal CS-potentiated feeding. By contrast, rats with lesions of the basolateral amygdala showed normal PIT but failed to display CS-potentiated feeding. Performances in a variety of comparison conditions suggested that both lesion effects reflected impairment of acquired motivational functions, rather than with attentional processes or the display of specific learned responses. Implications of the double dissociation of these two aspects of Pavlovian conditioned incentive motivation for amygdala function in associative learning are considered.     

Retrograde amnestic effects of inferotemporal and amygdaloid seizures upon conditioned suppression of lever-pressing in monkeys

Seizures induced electrically in the inferotemporal cortex, as monitored by EEG recording, produced retrograde amnestic effects upon the development of conditioned suppression of lever-pressing to a visual CS paired with shock US but not to a similarly paired auditory CS. The afterdischarges, which propagated to the amygdala among other structures, appeared to interfere with the association of the visual CS with the noxious US without blocking retention of information about the noxious US itself. By contrast, seizures induced in the amygdala, which showed a more variable pattern of propagation to inferotemporal cortex, produced no apparent retrograde amnestic effects.     

Transient inactivation of orbitofrontal cortex blocks reinforcer devaluation in macaques

The orbitofrontal cortex (OFC) and its interactions with the basolateral amygdala (BLA) are critical for goal-directed behavior, especially for adapting to changes in reward value. Here we used a reinforcer devaluation paradigm to investigate the contribution of OFC to this behavior in four macaques. Subjects that had formed associations between objects and two different primary reinforcers (foods) were presented with choices of objects overlying the two different foods. When one of the two foods was devalued by selective satiation, the subjects shifted their choices toward the objects that represented the nonsated food reward (devaluation effect). Transient inactivation of OFC by infusions of the GABA(A) receptor agonist muscimol into area 13 blocked the devaluation effect: the monkeys did not reduce their selection of objects associated with the devalued food. This effect was observed when OFC was inactivated during both satiation and the choice test, and during the choice test only. This supports our hypothesis that OFC activity is required during the postsatiety object choice period to guide the selection of objects. This finding sharply contrasts with the role of BLA in the same devaluation process (Wellman et al., 2005). Whereas activity in BLA was required during the selective satiation procedure, it was not necessary for guiding the subsequent object choice. Our results are the first to demonstrate that transient inactivation of OFC is sufficient to disrupt the devaluation effect, and to document a role for OFC distinct from that of BLA for the conditioned reinforcer devaluation process in monkeys.     

Lesions of the perirhinal cortex impair sensory preconditioning in rats

The effects of lesions of the perirhinal cortex on the development of associations between two conditioned stimuli (CSs) were examined with a sensory preconditioning procedure. Rats were given either bilateral electrolytic lesions of the perirhinal cortex or control surgery. They were then given either paired or unpaired presentations of a light CS and a tone CS. All of the rats were then given eyeblink conditioning procedures that involved paired presentations of either the light or tone and a periorbital shock unconditioned stimulus (US). The rats were finally given a test session that consisted of unpaired presentations of the tone and light CSs. Sensory preconditioning was established in the control group, but not in the lesion group. The findings are consistent with the view that the perirhinal cortex is involved in forming associations between neutral stimuli (even in the absence of reinforcement).     

The effects of selective amygdala, orbital frontal cortex or hippocampal formation lesions on reward assessment in nonhuman primates

We examined the effects of bilateral amygdaloid, hippocampal or orbital frontal cortex lesions on reward assessment in rhesus monkeys (Macaca mulatta). In Experiment 1, basic preferences for foods and inedible nonfoods were measured pre- and postsurgery. None of the lesions produced changes in animals' preferences for palatable foods or raw meat relative to presurgery, although amygdaloid or hippocampal lesions yielded increased preference for inedible nonfoods postsurgery. When the reinforcement value of each animal's highest-preferred food was decreased by selective satiation, only animals with neurotoxic orbital frontal cortex lesions continued to select the sated food. Experiment 2 measured the impact of each lesion on learning 60 concurrent discrimination problems and, then, on flexibly avoiding objects associated with sated foods in favour of objects associated with nonsated foods. None of the lesions affected concurrent discrimination learning, but animals with neurotoxic amygdala or aspiration orbital frontal lesions could not refrain from displacing items covering devalued foods. Only animals with orbital lesions also selected the devalued food beneath the object. The results indicate a functional dissociation for the amygdala and orbital frontal cortex in reward assessment, depending on the type of the reinforcer available (objects vs. food). Finally, this is the first study indicating that the hippocampal formation is involved in the assessment of familiar nonfoods, but not in judging the current value of unconditioned and conditioned reinforcers.     

Reduced amygdala-orbitofrontal connectivity during moral judgments in youths with disruptive behavior disorders and psychopathic traits

We used functional magnetic resonance imaging (fMRI) to investigate dysfunction in the amygdala and orbitofrontal cortex in adolescents with disruptive behavior disorders and psychopathic traits during a moral judgment task. Fourteen adolescents with psychopathic traits and 14 healthy controls were assessed using fMRI while they categorized illegal and legal behaviors in a moral judgment implicit association task. fMRI data were then analyzed using random-effects analysis of variance and functional connectivity. Youths with psychopathic traits showed reduced amygdala activity when making judgments about legal actions and reduced functional connectivity between the amygdala and orbitofrontal cortex during task performance. These results suggest that psychopathic traits are associated with amygdala and orbitofrontal cortex dysfunction. This dysfunction may relate to previous findings of disrupted moral judgment in this population.     

Lateral parabrachial nucleus lesions in the rat: aversive and appetitive gustatory conditioning

Previous research involving tests of innate preferences and aversions shows that bilateral ibotenic acid lesions of the visceral neurons located in the lateral parabrachial nucleus of the pons selectively disrupt consumption of those gustatory stimuli whose intake is augmented or restricted by their postoral consequences. The present study examined the performance of the same experimental subjects in learned preference and aversion tasks. The lesioned rats failed to develop a conditioned taste aversion (Experiment 1), a conditioned flavor preference (Experiment 2), and a conditioned aversion to the oral trigeminal stimulus, capsaicin (Experiment 3). The pattern of results from both types of taste-guided behaviors (innate and learned) suggests that excitotoxic lesions of the lateral parabrachial nucleus diminish sensitivity to gastrointestinal feedback which, in the present experiments, precludes aversive and appetitive associative learning.     

Place and taste aversion learning: role of basal forebrain, parietal cortex, and amygdala.

Animals with nucleus basalis magnocellularis (NBM), parietal cortex, dorsolateral frontal cortex, amygdala or control lesions were tested in a neophobia and taste aversion learning task. Only animals with basolateral amygdala lesions were impaired in taste aversion learning and in displaying neophobia to a novel flavor. This finding suggested a dissociation between the function of the NBM component of the basal forebrain cholinergic system and the amygdala. The same animals with NBM or control lesions were then tested for acquisition of a spatial navigation task using a dry-land version (cheese board) of the Morris water maze. Animals with NBM lesions were impaired in this task relative to control animals. Animals with parietal cortex lesions displayed a comparable deficit in the place navigation task. These findings suggest parallel functions for the NBM component of the basal forebrain system and the parietal cortex. The role of the NBM in mediating memory appears to be limited in that it does not play a role in all learning situations.     

Contribution of the amygdala, but not orbitofrontal or medial prefrontal cortices, to the expression of flavour preferences in marmoset monkeys

The development of food preferences contributes to a balanced diet, and involves both innate and learnt factors. By associating flavour cues with the reinforcing properties of the food (i.e. postingestive nutrient cues and innately preferred tastes, such as sweetness), animals acquire individual preferences. How the brain codes and guides selection when the subject has to choose between different palatable foods is little understood. To investigate this issue, we trained common marmoset monkeys (Callithrix jacchus) to respond to abstract visual patterns on a touch-sensitive computer screen to gain access to four different flavoured juices. After preferences were stable, animals received excitotoxic lesions of either the amygdala, the orbitofrontal cortex or the medial prefrontal cortex. Neither the orbitofrontal nor the medial prefrontal cortex lesions affected pre-surgery-expressed flavour preferences or the expression of preferences for novel flavours post-surgery. In contrast, amygdala lesions caused a shift in the preferences for juices expressed pre-surgery such that, post-surgery, juices were chosen according to their overall carbohydrate (simple sugars) content or 'sweetness'. Subsequent tests revealed that amygdala-lesioned animals only expressed juice preferences if they differed in 'sweetness'. Unlike controls, orbitofrontal cortex-lesioned and medial prefrontal cortex-lesioned animals, they were unable to display preferences between juices matched for 'sweetness' i.e. 5% sucrose solutions aromatised with different essential oils. The most parsimonious explanation is that the amygdala contributes to the expression of food preferences based on learnt cues but not those based on an innate preference for sweetness.     

Conditioned enhancement of antibody production is disrupted by insular cortex and amygdala but not hippocampal lesions.

Pavlovian conditioning procedures can be used to activate the immune system. A reliable conditioned increase of antibody production can be obtained in rats that have previously received a gustative or odor stimulus as the conditioned stimulus paired with an antigen, by exposing the animals to the conditioned stimulus alone. We showed evidence that an excitotoxic lesion bilaterally applied into the insular cortex or the amygdala, but not into the dorsal hippocampus, impaired the acquisition of both odor and gustatory conditioned immune enhancement. We found no effects of lesions on normal antibody production. These results suggest that the amygdala and the insular cortex are involved in the neural-immune interactions that mediate conditioned immunity.     

Reduced amygdala–orbitofrontal connectivity during moral judgments in youths with disruptive behavior disorders and psychopathic traits

We used functional magnetic resonance imaging (fMRI) to investigate dysfunction in the amygdala and orbitofrontal cortex in adolescents with disruptive behavior disorders and psychopathic traits during a moral judgment task. Fourteen adolescents with psychopathic traits and 14 healthy controls were assessed using fMRI while they categorized illegal and legal behaviors in a moral judgment implicit association task. fMRI data were then analyzed using random-effects analysis of variance and functional connectivity. Youths with psychopathic traits showed reduced amygdala activity when making judgments about legal actions and reduced functional connectivity between the amygdala and orbitofrontal cortex during task performance. These results suggest that psychopathic traits are associated with amygdala and orbitofrontal cortex dysfunction. This dysfunction may relate to previous findings of disrupted moral judgment in this population.