Potentiation of latent inhibition

Rats were given exposure either to an odor (almond) or a compound of odor plus taste (almond plus saline), prior to training in which the odor served as the conditioned stimulus. It was found, for both appetitive and aversive procedures, that conditioning was retarded by preexposure (a latent inhibition effect), and the extent of the retardation was greater in rats preexposed to the compound (i.e., latent inhibition to the odor was potentiated by the presence of the taste). In contrast, the presence of the taste during conditioning itself overshadowed learning about the odor. We argue that the presence of the salient taste in compound with the odor enhances the rate of associative learning, producing a rapid loss in the associability of the odor. This loss of associability will generate both overshadowing and the potentiation of latent inhibition that is observed after preexposure to the compound.     

Extinction and latent inhibition of within-event learning are context specific

Exposure to a solution composed of an odor (almond) and a taste (salt) produced a context-independent preference when rats were subsequently tested with almond under a salt appetite. Postcompound exposure to either the almond or the salt alone reduced almond preferences but only when rats were tested in the extinction context. Exposure to either the almond or the salt in 1 context in advance of exposure to the compound in a different context also reduced preferences but only when the rats were tested in the context in which the element had been pre-exposed. These results show that extinction and latent inhibition of within-event learning are context specific.     

Bilateral lesions of the insular cortex or of the prefrontal cortex block the association between taste and odor in the rat

The neural basis for the association between taste and odor was investigated in the rat. First, behavioral procedures to study the mechanisms underlying the association between qualitative aspects of the odor and taste in rats were developed. Rats were presented with several pairings of the 0.3 mol/L NaCl solution and a flavor, and pairings of distilled water and another flavor. Then the rats received an IP injection of a furosemide to develop sodium deficiency. On the next day, the rats were presented with either of two types of odor-flavored water: water in which the flavor had been paired with NaCl, or water in which the flavor (grape or coffee) had been paired with distilled water. Normal rats avoided ingesting the water flavored with the odor previously paired with NaCl. Sodium-deprived rats, however, ingested the water flavored with that odor. Rats with lesions in either the insular cortex or in the prefrontal cortex neither preferred nor avoided the water flavored with the odor paired with NaCl. It was concluded that rats acquire association between taste and odor, and that the insular and the prefrontal cortices of the rats were involved in this association.     

Motivational state regulates the content of learned flavor preferences

Rats acquired a preference for an aqueous odor (almond) presented in simultaneous compound with sucrose. Separate presentations of saccharin reduced this preference in rats with ad-lib access to food during training or at test, but not in rats that were hungry during both training and test. In contrast, separate presentations of sucrose reduced the preference for the almond irrespective of deprivation state during training and test. We interpret the results to mean that a hungry rat forms odor-taste and odor-calorie associations, and its motivational state on test determines which of these associations controls the preference. In contrast, a rat that is not hungry during training only forms an odor-taste association, and its performance on test is independent of its level of hunger.     

Temporary basolateral amygdala lesions disrupt acquisition of socially transmitted food preferences in rats

Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in chemosensory learning remains somewhat controversial. In particular, it has been suggested that the amygdala may not be involved in a form of chemosensory learning that has recently received a substantial amount of study-socially transmitted food preference (STFP). Here, we provide evidence for this involvement by pharmacologically inactivating the basolateral amygdala bilaterally during STFP training. The same inactivation sites that impaired taste aversion learning eliminated the normally conditioned preference for a food smelled on a conspecific's breath. Impairments of learned preference persisted even in testing sessions in which BLA was not inactivated, and learning was normal when the BLA was inactivated only during testing sessions; thus, the impairment was a true acquisition deficit. In conjunction with previous results from other paradigms, therefore, our data suggest that the amygdala is vital for learning procedures involving pairings of potent and arbitrary chemosensory stimuli.     

Development switch in neural circuitry underlying odor-malaise learning

Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.     

Recognition memory for social and non-social odors: differential effects of neurotoxic lesions to the hippocampus and perirhinal cortex

The contributions of the hippocampus (HC) and perirhinal cortex (PER) to recognition memory are currently topics of debate in neuroscience. Here we used a rapidly-learned (seconds) spontaneous novel odor recognition paradigm to assess the effects of pre-training N-methyl-D-aspartate lesions to the HC or PER on odor recognition memory. We tested memory for both social and non-social odor stimuli. Social odors were acquired from conspecifics, while non-social odors were household spices. Conspecific odor stimuli are ethologically-relevant and have a high degree of overlapping features compared to non-social household spices. Various retention intervals (5 min, 20 min, 1h, 24h, or 48 h) were used between study and test phases, each with a unique odor pair, to assess changes in novelty preference over time. Consistent with findings in other paradigms, modalities, and species, we found that HC lesions yielded no significant recognition memory deficits. In contrast, PER lesions caused significant deficits for social odor recognition memory at long retention intervals, demonstrating a critical role for PER in long-term memory for social odors. PER lesions had no effect on memory for non-social odors. The results are consistent with a general role for PER in long-term recognition memory for stimuli that have a high degree of overlapping features, which must be distinguished by conjunctive representations.     

Weanling and senescent rats process simultaneously presented odor and taste differently than young adults

Weanling, young-adult, and senescent Wistar albino rats had a novel odor/taste stimulus or a single taste stimulus either paired or explicitly unpaired with the unconditioned stimulus, lithium chloride. Animals were then given a saccharin vs water preference test. Standard preference scores indicated that the odor competed with taste for association with the US in young-adult rats but potentiated the conditioned aversion to taste in weanling and senescent rats. Results were interpreted in terms of age-related attentional differences which were hypothesized to account for infantile amnesia and for the memory dysfunction typically observed in senescent animals.     

Contribution of the dorsal subiculum to memory for temporal order and novelty detection using objects,odors, or spatial locations in the rat

The contribution of the dorsal subiculum (DS) to memory for temporal order and novelty detection was assessed using a spontaneous exploration paradigm with objects (visual/tactile stimuli), odors, or spatial locations (Hunsaker, Fieldsted, Rosenberg, & Kesner, 2008). Rats with selective excitotoxic lesions of the DS were compared to sham-operated rats (SHAM) in the two exploration tests. In temporal order tests, two previously explored stimuli were presented and normal rats typically show a preference for exploring the stimulus that was first explored compared to the other stimulus. In novelty detection tests, a familiar and a new stimulus were presented and normal rats typically have a preference for exploring new stimuli. In temporal order tests, results indicated that Group SHAM explored significantly more the first than the last stimulus they met when the stimuli were odors or objects. In addition, SHAM rats predictably displayed a significant preference for the new stimulus in the novelty detection tests with objects, odors, and spatial locations. Group DS did not differ from controls on the temporal order and the novelty detection tests with objects or odors. However, on the novelty detection test with spatial locations, Group DS differed from Group SHAM. These results suggest that the DS is necessary for the memory of spatial locations but not of objects and odors.     

Recognition of conspecific odors by laboratory rats (Rattus norvegicus) does not show context specificity

This experiment investigated how contextual cues affect recognition of conspecific odors in laboratory rats (Rattus norvegicus). Rats received 5 encounters with the same odor in the same context. For the 6th test encounter, all rats received a simultaneous presentation of the original odor and a novel odor. The authors tested 1 group of rats (context same) in the same context as before. For the remaining 2 groups, the test encounter was in a different context that 1 group (context different) had experienced but that 1 group (context novel) had not. A significant preference to investigate the novel odor by context-same and context-different rats, but not by context-novel rats, suggests that odor recognition can occur following transfer to a different, but familiar, test context, indicating a lack of context specificity.     

Conditioned taste and taste-potentiated odor aversions in the Syracuse high- and low-avoidance (SHA/Bru and SLA/Bru) strains of rats (Rattus norvegicus).

Syracuse high- and low-avoidance Long-Evans rats (Rattus norvegicus; SHA/Bru and SLA/Bru) were selectively bred for good and poor active-avoidance learning. However, SLA/Bru animals are superior to SHA/Bru rats in conditioned suppression and passive avoidance learning. In this experiment, saccharin taste and almond odor were the components of a compound conditioned stimulus (flavor) in an illness-induced aversive conditioning paradigm. SLA/Bru rats (n = 17) showed stronger conditioned flavor, taste, and odor aversion than did SHA/Bru animals (n = 18). Unselected Long-Evans rats (n = 18) were intermediate between the selected strains. SLA/Bru and Long-Evans rats showed taste-potentiated odor aversions in this experiment, whereas SHA/Bru animals did not. The results provide evidence that genetic factors, as exemplified by the different strains, are importantly involved in the mechanisms underlying interoceptive and exteroceptive aversive conditioning.     

Extinction of Within-event Learning Is Contextually Controlled and Subject to Renewal

Five experiments examined within-event learning in rats by inducing an appetite for one of the elements (salt) of a compound stimulus and assessing preference for the other element (almond). Almond preference was conditional upon (1) the almond flavour having been presented in compound with the salt, and (2) the assessment being conducted when the rats were out of sodium balance (Experiment 1). Presentations of the compound in one environment (A) and of the salt and almond elements in a second environment (B) resulted in greater almond preference when rats were tested in A than in B (Experiment 2). Almond preference was reduced when separate presentations of the compound and almond (Experiment 3) or of the compound and salt (Experiment 4) occurred in the same environments but not when these presentations occurred in different environments. Rats exposed to the compound in A and then extinguished to the elements in either A or B showed a reduced almond preference when tested in the extinction environment, but not when tested in the other environment (Experiment 5). Thus, extinction of within-event learning is context-specific and subject to renewal. The results were interpreted in terms of an associative model whereby separate presentations of the elements result in a symmetrical inhibitory link which is contextually gated (Bouton, 1993).     

Interactions between conditioned and unconditioned flavor preferences

Five experiments investigated how rats' conditioned preferences or aversions for aqueous odors paired with sucrose or salt are affected by their unconditioned response to those tastes. Rats preferred an odor paired with 30% sucrose over an odor paired with 5% sucrose when both were presented in 5% sucrose, but they showed no preference or, if thirsty, showed the reverse preference, when the odors were presented in 30% sucrose. These changes in conditioned preference corresponded to changes in the rats' unconditioned preference for the accompanying sucrose solution. Rats' conditioned aversions for odors paired with salt showed a similar dependence on their reaction to the accompanying salt solution. The results were interpreted as showing that conditioned and unconditioned flavor preferences combine additively, as if mediated by the same sensory representation.     

Olfactory discrimination, reversal learning, and stimulus control in rats.

Rats were trained to discriminate lights, tones, or odors and then given a series of discrimination reversals. Only rats trained with odors showed positive transfer on the first reversal and acquisition of a reversal set. Other experiments demonstrated that rats preferentially attend to odors when presented in compound with lights or tones; that odors exert more discriminative control than tones in tests using compound stimuli of competing sign; and that after pretraining on the positive stimulus, acquisition of an odor but not a light discrimination occurs with virtually no errors. These results demonstrate the importance of stimulus modality in the establishment of stimulus control and the need for more careful analysis of stimulus factors in cross-species comparisons of learning ability.     

Lesions of orbitofrontal cortex and basolateral amygdala complex disrupt acquisition of odor-guided discriminations and reversals

Recent work indicates that both orbitofrontal cortex (OFC) and the basolateral complex of the amygdala (ABL) are involved in processes by which cues are associated with predicted outcomes. To examine the respective roles of these structures in discrimination learning, rats with bilateral sham or neurotoxic lesions of either OFC or ABL were trained on a series of four 2-odor discrimination problems in a thirst-motivated go, no-go task. After acquisition of the series of odor problems, the rats were trained on serial reversals of the final odor problem. Performance on each problem was assessed by monitoring accuracy of choice behavior, and also by measuring latency to respond for fluid outcomes after odor sampling. During discrimination learning, rats in both lesioned groups had similar deficits, failing to show normal changes in response latency during learning, while at the same time exhibiting normal choice behavior relative to controls. Choice behavior was affected only during the reversal phase of training, in which OFC and ABL lesions produced distinctive deficits. Rats with ABL lesions were impaired on the first reversal (S1−/S2+), but were unimpaired at acquiring a reversal back to the original odor-outcome contigencies (S1+/S2−), whereas rats with OFC lesions were impaired on both types of reversals. These findings suggest that OFC and ABL serve partially overlapping roles in the use of incentive information that supports normal discrimination performance.     

Odor from rats tasting a signal of illness

Rats running in a runway emit discriminable odors when encountering reward (R) or nonreward (N) goal events, and subsequent rats use these odors as discriminative stimuli to alter their approach speeds. In the present studies, a third goal event, aversively conditioned denatonium saccharide (A), was introduced. In Experiment 1, rats evidently emitted an odor when encountering the A goal event, because in the presence of this A odor subsequent conspecifics slowed their approach to the goal, much like their behavior on N trials. In Experiment 2, when N odor signaled R goal events and A odor signaled A goal events, rats approached quickly to N but slowly to A, indicating that they could discriminate N and A odors at the given concentrations. These studies indicate that rats emit an odor when confronted with a signal of impending illness and that this odor seems readily discriminable from R and N odors.     

Complementary roles for the amygdala and hippocampus during different phases of appetitive information processing

Evidence collected from rodent models of memory storage suggests that rapid forms of learning engage the involvement of multiple brain regions each of which may participate in a different component of information processing. The present study used temporary inactivation of the amygdala and hippocampus during different phases of information processing on a one-trial appetitive-conditioning task to examine how these two regions might participate in the storage of appetitive memories. Male Long Evans rats were chronically implanted into the amygdala or dorsal hippocampus and food deprived. Rats were trained on a radial maze conditioned cue preference task where training occurred in one 40-min session and testing took place 24 h later. The amygdala or hippocampus was inactivated separately with muscimol (50 ng/microl) injected immediately before or after training, or immediately before testing. Saline-injected rats displayed a conditioned preference by spending more time in the arm that previously contained food than in the arm that did not contain food. Muscimol injected into the amygdala before training or testing blocked the conditioned preference. Muscimol injected into the hippocampus immediately after training blocked the conditioned preference. These results suggest that the processing of memories may require multiple contributions from separate brain systems for at least short-term (24 h) storage. The resulting output from each system may converge on a similar downstream target to influence behavior.     

Potentiation of odor by taste in rats: tests of some nonassociative factors

The contribution of nonassociative neophobia and sensitization to the potentiation of odor by taste in rats was tested in three experiments. In Experiment 1, neophobia for almond odor (O), saccharin taste (T), and odor-taste compound (OT) cues was tested before and after noncontingent lithium chloride poisoning and compared with conditioned aversions produced by OT-LiCl temporal pairing. The OT compound potentiated unconditioned neophobia, but there was no evidence of poison-enhanced neophobia, disinhibition of neophobia, or sensitization by noncontingent LiCl; temporal pairing produced aversions for the compound and its elements. In Experiment 2, generalization to a novel odor was tested after O-LiCl or compound OT-LiCl pairing. The potentiated odor aversion did not generalize to the novel odor; it was specific to the odor paired with taste and LiCl. In Experiment 3, potentiation of the odor component by a discriminant or nondiscriminant taste component was tested. Potentiation was evident only when a novel discriminant taste was in compound with odor prior to LiCl poisoning. These studies support an associative "indexing" hypothesis of the potentiation effect in rats.     

Involvement of the insular cortex in retention of conditioned taste aversion is not time dependent

In fear-associated learning paradigms, hippocampal lesions induce memory deficits of recent but not remote memories, while amygdala lesions produce retention deficits irrespective of the age of the memory. In conditioned taste aversion (CTA), non-hippocampal mediated learning paradigm, the insular vortex (IC) has shown to have a crucial role in consolidation and storage of CTA memory. Due to the functional and anatomical similarities to the hippocampus, a time dependent role of the IC in CTA retention cannot be ruled out. To test whether the IC shows a time dependent role in CTA memory retention, male Wistar rats were CTA trained on saccharin 0.1% (LiCl 0.15M, 2% b/w, 40 min after drinking) and lesioned with ibotenic acid (200-300 nL, 5mg/mL) unilaterally into the IC 1 week or bilaterally 1 or 6 weeks after CTA. CTA memory was completely disrupted in both bilateral lesion groups but unaffected in the unilateral lesioned group. The resulting preference was comparable to that of the bilaterally IC lesioned animals exposed to the taste for the first time, proving that in these animals a complete amnesic state was achieved. Bilaterally IC lesioned rats showed normal discrimination between preferred (sucrose 5%) and non-preferred (quinone) tastes. Our data indicates that the involvement of the IC in CTA is not time dependent and that CTA memories are stored in each hemisphere separately.     

Verbal memory elicited by ambient odor.

This study examined whether an ambient odor can act as a contextual cue for retrieval of verbal stimuli. Subjects (N = 47) learned a list of 24 words while exposed to one of two odors (either jasmine incense or Lauren perfume) and subsequently relearned the list with either the same or the alternative odor present. Superior memory for the word list was found when the odor present during the relearning session was the same one that had been present at the time of initial learning, thereby demonstrating context-dependent memory. There were no differences in initial learning between the two odor conditions. No differences in pleasantness or intensity were found between the odors.