Odor Conditioned Stimulus Research Articles

Commentary

HIGHLIGHTED TOPICSCommentaryGary C. Sieck, Gary C. Sieck Journal of Applied Physiology, EditorPublished Online:01 Feb 2003https://doi.org/10.1152/japplphysiol.01065.2002MoreSectionsPDF (21 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat It is often assumed that the control of breathing is influenced by learning and memory processes, thus reflecting a high level of functional plasticity. Conditioned respiratory responses are regarded as an adaptive feedforward mechanism of breathing control that anticipates metabolic needs. According to this view, such conditioned behaviors are acquired in the early postnatal period. The firstHighlighted Topics article featured in this issue of theJournal of Applied Physiology, “Classical conditioning of breathing pattern after two acquisition trials in 2-day-old mice,” by Durand et al., examined conditions of breathing patterns in neonatal mice. The conditioning paradigm used in this study involved an artificial odor conditioned stimulus, signaling a natural unconditioned stimulus based on maternal care. Durand and colleagues had previously shown that classical conditioning of breathing patterns by a sensory conditioned stimulus with hypercapnia or hypoxia as the unconditioned stimulus was effective in adult animals (J Appl Physiol83: 1174–1183, 1997; Behav Neurosci 112: 1393–1401, 1998, Behav Brain Res 106: 29–37, 1999) and humans (J Appl Physiol 70: 676–682, 1991). The conditioned stimulus was presented either 30 min before contact with the mother (control unpaired group) or at the time of contact with the mother (experimental paired group). Conditioning was tested by measuring the respiratory response to the conditioned stimulus, using whole-body plethysmography. These investigators found significantly stronger ventilatory responses to the conditioned stimulus in the experimental group compared with that shown in controls, due to the strong conditioning effect on tidal volume and the smaller conditioning effect on respiratory rate. Because there were no significant between-group differences in somatomotor activity, it is likely that the respiratory conditioned stimulus was caused by higher metabolic demands in the experimental pups compared with that in controls. This behavioral respiratory response expressed a learned association between environmental stimuli.These results demonstrate that breathing is sensitive to conditioning. In addition, these results indirectly support the hypothesis that learned feedforward processes may complement feedback pathways during postnatal maturation of respiratory control. Furthermore, the fact that breathing appeared to be a more sensitive index of associative learning than somatomotor activity may have important practical implications for assessment of learning abilities in newborn mice.Activity-dependent neuroplasticity, demonstrated throughout the central nervous system (CNS), has been more recently documented in respiratory motoneuron networks. One of the challenges has been to determine the physiological or pathophysiological conditions during which plasticity in the central network might become important. The second article featured in this issue, “Neuroplasticity in nucleus tractus solitarius neurons after episodic ozone exposure in infant primates,” by Chen et al., found that repeated exposure of infant primates to ozone, a physiologically relevant environmental pollutant, resulted in neuroplasticity in the nucleus tractus solitarius (NTS), the CNS gateway for viscerosensory input that can shape respiratory motor pattern. The NTS neurons exhibited a persistent increase in intrinsic excitability, but at the same time, as a group, these neurons were less responsive to synaptic activation by stimulation of sensory afferent fibers in the tractus solitarius. Endogenous substance P, which has also been implicated in plasticity of the cell bodies of lung sensory afferent fibers, contributed to the ozone-induced increase in excitability. This study demonstrated that repeated exposure to an inhaled pollutant can result in complex changes in both the intrinsic and synaptic properties of neurons in the cardiorespiratory region of the NTS. In the context of the present study, the diminished responsiveness to stimulation of the tractus solitarius may help to explain adaptation of reflex respiratory motor responses to repeated ozone exposures. This adaptation may contribute to detrimental effects of irritants and particles on lung function by diminishing respiratory motor protective responses of apnea, cough, and rapid breathing. On the other hand, the enhanced intrinsic excitability of NTS neurons may modify respiratory motor output from pathways that do not depend exclusively on sensory input. The mechanisms by which the pollutant causes changes and the implication of these changes in health and disease remain to be studied.FOOTNOTES10.1152/japplphysiol.01065.2002This article has no references to display. Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByModulation of hypoglossal motoneuron excitability by intracellular signal transduction cascadesRespiratory Physiology & Neurobiology, Vol. 147, No. 2-3 More from this issue > Volume 94Issue 2February 2003Pages 811-811 Copyright & PermissionsCopyright © 2003 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.01065.2002History Published online 1 February 2003 Published in print 1 February 2003 Metrics

Behavioral expression of learned fear in rats is appropriate to their age at training, not their age at testing.

Recent research has shown that learned fear emerges in a response-specific sequence. For example, an odor conditioned stimulus (CS) previously paired with shock elicits behavioral expressions of fear like avoidance at a younger age than it elicits other behavioral expressions of fear like potentiation of the startle response (Richardson, Paxinos, & Lee, 2000). In the present study, the question of whether learned fear is expressed in a manner appropriate to the animal's age at training or its age at testing was explored in three experiments, all using a within-subjects design. The results suggest that learned fear is expressed in a manner appropriate to the rat's age at training, not its age at testing. The Discussion section focuses on the implications of these findings for (1) the developmental analysis of memory and (2) the idea that an aversive CS elicits a central state of fear.

Behavioral conditioning of the immune system

Publisher Summary Both animal and human studies reveal that immune-system activity can be modulated by behavioral conditioning. Unconditioned stimuli (US) are pharmacological regulators of immune system activity, which are variously stimulatory or inhibitory to aspects of immune function. This might properly be termed “behavioral immunopharmacological conditioning.” Antigen challenges to the immune system can also serve as the US such that on representation of a conditioned stimulus (CS), an enhanced immunological response is observed. In studies of the rat, a gustatory or odor CS can induce, in terms of specific antibody titer and isotype, the characteristics of a secondary response to a protein antigen challenge. The mechanism by which conditioning of the immune system occurs has only been partly explored although it is clear that no single mechanism could possibly be responsible for all of the observed effects. This merely reflects the complexity of both the nervous and the immune systems and their interrelatedness. A primary efferent pathway from the brain to the immune system is the neuroendocrine hypothalamic–pituitary–adrenal (HPA) axis, and it is clear that activation of the HPA axis and secretion of corticosterone can be conditioned and that some of the conditioning paradigms described in this chapter condition its activation in conjunction with conditioning of some aspect of immunity.

Effect of an amino acid on feeding preferences and learning behavior in the honey bee, Apis mellifera

Amino acids are common constituents of floral nectars and can be critical components in the diets of insect pollinators. Yet the means through which insects detect amino acids can be complex and arise from pre- and post-ingestive mechanisms. Furthermore, the response to an amino acid can change depending on an insect's nutritional status. Here we use a sensitive feeding assay and Proboscis Extension Response (PER) conditioning in the honey bee to assay the effect of glycine, which is a common constituent of nectars and pollens. Subjects preferred to feed on a sucrose stimulus that contained glycine, and the highest relative preference was recorded for the highest concentration of glycine. However, the highest response rate occurred at lower than maximal concentrations and differed depending on the physiological status of the subjects. These results are consistent with a model in which subjects attempt to maintain a physiological target amount of glycine/amino acid relative to other nutrients. All concentrations of glycine enhanced the rate and magnitude of a conditioned response to an odor in the PER assay, which demonstrates that animals can learn to modify their responses to an odor conditioned stimulus based on the presence of amino acid. This capability would enhance a honey bee's ability to evaluate the quality of floral nectars, which are associated with, among other things, odor cues given off by flowers. In future studies these techniques will allow us to evaluate the physiological roles that amino acids play in honey bee diet and choice behavior.

Retroactive revaluation of an odor-taste association

Rats showed an increase or decrease in preference for an aqueous odor conditioned stimulus (CS) presented in compound with a palatable (sucrose) or unpalatable (quinine) taste unconditioned stimulus (US), respectively. Four experiments then studied the consequences for odor preference of presenting water in the context where the odor-taste compound had previously occurred (i.e., no-CS-no-US experience). Exposure to that context increased the preference for the odor associate of sucrose and decreased preference for the odor associate of quinine. The increased preference for the odor associate of sucrose was contingent on reexposure to the context where the odor-sucrose compound had occurred (i.e., retroactive revaluation) and was reduced by preexposure to the context where the odor-sucrose compound was to occur (i.e., latent inhibition of the context). The retroactive revaluation of within-event learning caused by exposures to the associated context is discussed in terms of (1) the modified version of the SOP model (Wagner, 1981) proposed by Dickinson and Burke (1996) and (2) the comparator model (Miller & Matzel, 1988).

Olfactory Cues and Morphine-Induced Conditioned Analgesia in Rats

In a Pavlovian conditioning procedure, rats were exposed to an odor conditioned stimulus (CS) and then were given morphine with its effect serving as the unconditioned stimulus (US). After four CS-US pairings, the CS was tested alone to assess the presence of an analgesic conditioned response (CR) using a hot-plate test. In Experiment 1a, two groups were conditioned by pairing either 10 mg/kg morphine or saline with an odor CS. In Experiment 1b, two groups were given an odor CS paired or unpaired with 10 mg/kg morphine. These results established that an odor cue can support a morphine-induced analgesic CR. Experiment 2 characterized the dose–effect curve (0, 3, 10, and 30 mg/kg morphine) using an odor conditioning procedure. The dose–effect curve showed an inverted U-shaped function, with the 10 mg/kg morphine group having significantly longer paw-lick latencies compared to all other groups. This finding contrasts with the monotonically ascending dose–effect curve for the analgesic unconditioned response (UR) to morphine.

A Pavlovian analysis of food-attraction conditioning in the snailHelix aspersa

Following brief pairing of an odor with a feeding experience (food-attraction conditioning), snails will lower their tentacles when subsequently presented with that odor alone. Three experiments investigated the possible behavioral mechanism mediating food-attraction conditioning in the snailHelix aspersa. It is suggested that food-attraction conditioning is an example of Pavlovian conditioning. In this case, the odor (conditioned stimulus) is paired with oral stimulation (unconditioned stimulus), which elicits lowering of the tentacles (unconditioned response). Following conditioning, the odor comes to elicit lowering of the tentacles (conditioned response). Experiment 1 ruled out nonassociative effects, such as habituation and sensitization, using an unpaired control group. Experiment 2 provided further evidence against a role for habituation of neophobia, through the demonstration of extinction following conditioning. In Experiment 3, an omission procedure was used to rule out the possible role of instrumental contingencies.

Odor-guided fear conditioning in rats: 2. Lesions of the anterior perirhinal cortex disrupt fear conditioned to the explicit conditioned stimulus but not to the training context.

Previous studies examining the neural substrates of fear conditioning have indicated unequivocally that the acquisition and expression of conditioned fear depends critically on the integrity of the amygdala. The extent to which the rhinal cortical areas contribute to fear conditioned to either the explicit conditioned stimulus (CS) or to the training context is less clear, however. The effects of pretraining lesions of the anterior perirhinal (PRH) cortex on fear conditioned to an explicit odor CS and to the context in which CS-unconditioned stimulus pairing took place was examined in rats. Rats with PRH cortex lesions demonstrated a robust attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data suggest that the PRH cortex is an important component of the neural system supporting the association between olfactory cues and footshock and add to a growing body of evidence implicating the rhinal cortical regions in associative learning.

Odor-guided fear conditioning in rats: 2. Lesions of the anterior perirhinal cortex disrupt fear conditioned to the explicit conditioned stimulus but not to the training context.

Previous studies examining the neural substrates of fear conditioning have indicated unequivocally that the acquisition and expression of conditioned fear depends critically on the integrity of the amygdala. The extent to which the rhinal cortical areas contribute to fear conditioned to either the explicit conditioned stimulus (CS) or to the training context is less clear, however. The effects of pretraining lesions of the anterior perirhinal (PRH) cortex on fear conditioned to an explicit odor CS and to the context in which CS-unconditioned stimulus pairing took place was examined in rats. Rats with PRH cortex lesions demonstrated a robust attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data suggest that the PRH cortex is an important component of the neural system supporting the association between olfactory cues and footshock and add to a growing body of evidence implicating the rhinal cortical regions in associative learning.

Conditioning of body temperature and natural killer cell activity with arecoline, a muscarinic cholinergic agonist.

Arecoline, a muscarinic cholinergic agonist, was found to depress body temperature and elevate the activity of preactivated natural killer (NK) cells. To demonstrate that the unconditioned responses produced by arecoline were mediated through central nervous system pathways, we used the drug as an unconditioned stimulus. By pairing camphor odor (conditioned stimulus) with arecoline (unconditioned stimulus), it was possible to simultaneously condition both a decrease in body temperature and augmentation of NK cell activity. The observations suggest that although both the modulation of body temperature and NK cell activities are integrated at the level of the hypothalamus, these pathways of regulation can be differentiated.

Sodium carbonate prevents NK cell conditioning by interfering with the US signal.

The conditioned enhancement of natural killer (NK) cell activity can be blocked by the injection of sodium carbonate solution prior to the association of the camphor odor conditioned stimulus (CS) with the polyinosinic:polycytidylic acid (poly I:C) unconditioned stimulus (US). We have experimentally dissociated the memory which is formed for camphor odor from that developed for the association of camphor with the US. The memory for the odor of camphor can be allowed to develop one day before the administration of the unconditioned stimulus. Sodium carbonate appears to act within the central nervous system to block the association of the unconditioned stimulus with the conditioned stimulus. The data also suggest that in conditioning of NK cell activity, there are two specific sites for memory of the response, one for the conditioned stimulus and the other for the association of the unconditioned stimulus with the conditioned stimulus.

An identified neuron mediates the unconditioned stimulus in associative olfactory learning in honeybees

DURING classical conditioning, animals learn to associate a neutral stimulus with a meaningful, or unconditioned, stimulus. The unconditioned stimulus is essential for forming associations, and modifications in the processing of the unconditioned stimulus are thought to underlie more complex learning forms1–4. Information on the neuronal representation of the unconditioned stimulus is therefore required for understanding both basic and higher-order features of conditioning. In honeybees, conditioning of the proboscis extension reflex occurs after a single pairing of an odour (conditioned stimulus) with food (unconditioned stimulus)5,6 and shows several higher-order features of conditioning6–8. I report here the identification of an interneuron that mediates the unconditioned stimulus in this associative learning. Its physiology is also compatible with a function in complex forms of associative learning. This neuron provides the first direct access to the cellular mechanisms underlying the reinforcing properties of the unconditioned stimulus pathway.

Serotonergic influence on olfactory learning in the neonate rat

The role of the serotonergic innervation of the olfactory bulb was examined in neonate rat pups (Sprague-Dawley) by utilizing an olfactory learning paradigm (Sullivan, McGaugh, & Leon, 1991; Sullivan, Wilson, & Leon, 1989). One hundred fifty nanoliters of the neurotoxin 5,7-dihydroxytryptamine (5,7-dHT, 10 micrograms/microliters) was injected into each anterior olfactory nucleus of Postnatal Day 2 (PND 2) pups in order to selectively deplete the serotonergic (5-HT) innervation of the olfactory bulb. On PND 8, control, sham-operated, or 5-HT-depleted pups were presented with stroke (unconditioned stimulus) paired with peppermint odor (conditioned stimulus) or were presented with peppermint alone. Other pups remained naive, i.e., they were not presented with either stroke or odor. The following day, the pups were placed on a mesh screen above two boxes containing either fresh bedding or bedding with peppermint odor for five 1-min trials. Control and sham-operated pups that were previously trained by the odor/stroke paradigm spent significantly more time over the peppermint odor than similarly trained 5-HT-depleted pups, pups trained using the odor only paradigm, or naive pups. Immunocytochemistry verified that the 5,7-dHT injections specifically depleted the 5-HT innervation of the olfactory bulb and left the 5-HT innervation of more caudal levels of the neuraxis (e.g., piriform cortex) intact. The locomotor behavior of the pups was not affected by the 5-HT depletions. This study is the initial investigation to suggest that 5-HT innervation to the olfactory bulb is important in the acquisition or expression of olfactory-based learned behavior in the neonate rat.

Neural correlates of olfactory learning paradigms in an identified neuron in the honeybee brain

1. Sensitization and classical odor conditioning of the proboscis extension reflex were functionally analyzed by repeated intracellular recordings from a single identified neuron (PE1-neuron) in the central bee brain. This neuron belongs to the class of "extrinsic cells" arising from the pedunculus of the mushroom bodies and has extensive arborizations in the median and lateral protocerebrum. The recordings were performed on isolated bee heads. 2. Two different series of physiological experiments were carried out with the use of a similar temporal succession of stimuli as in previous behavioral experiments. In the first series, one group of animals was used for a single conditioning trial [conditioned stimulus (CS), carnation; unconditioned stimulus (US), sucrose solution to the antennae and proboscis), a second group was used for sensitization (sensitizing stimulus, sucrose solution to the antennae and/or proboscis), and the third group served as control (no sucrose stimulation). In the second series, a differential conditioning paradigm (paired odor CS+, carnation; unpaired odor CS-, orange blossom) was applied to test the associative nature of the conditioning effect. 3. The PE1-neuron showed a characteristic burstlike odor response before the training procedures. The treatments resulted in different spike-frequency modulations of this response, which were specific for the nonassociative and associative stimulus paradigms applied. During differential conditioning, there are dynamic up and down modulations of spike frequencies and of the DC potentials underlying the responses to the CS+. Overall, only transient changes in the minute range were observed. 4. The results of the sensitization procedures suggest two qualitatively different US pathways. The comparison between sensitization and one-trial conditioning shows differential effects of nonassociative and associative stimulus paradigms on the response behavior of the PE1-neuron. The results of the differential conditioning procedure reveal that the effect observed for the one-trial conditioning paradigm is of an associative nature and that there might be modulations, which are specific for single and multiple trial conditioning procedures. It is hypothesized that the PE1-neuron is a possible element involved in the short-term acquisition, rather than in the long-term storage, of an associative olfactory memory in the honeybee.

A Simple, Single, Trial-Learning Paradigm for Conditioned Increase in Natural Killer Cell Activity

A change in natural killer (NK) cell activity can be conditioned with one trial learning when conditioned stimulus (CS) precedes the unconditioned stimulus (US). To avoid the problems associated with two reexposures in our earlier studies, we have developed a reliable and simple conditioning protocol utilizing the one trial learning and one reexposure to the odor CS. The conditioned change in NK cell activity was significantly different (P less than 0.05) from the control groups of mice. The paradigm is short and simple in that the conditioned change could be demonstrated within 3 days. We have also compared the effects of temporal association of CS and US on conditioned increase in NK cell activity. Forward conditioning (CS preceded the US) demonstrated a conditioned change, but the backward conditioning protocol did not. The paradigm provides a reliable approach to the study of mechanisms of the phenomenon of odor-NK conditioning.

The direction of the conditioned natural killer cell response can be re-directed with indomethacin and/or handling.

We have used the pairing of camphor odor conditioned stimulus (CS) and injection of poly I:C unconditioned stimulus (US) in a short 3 day single trial conditioning paradigm. Conditioning was done by exposing mice to the CS/US combination on day 0 and reexposing the conditioned animals to the CS on day 2. This results in a conditioned augmentation of the natural killer (NK) cell response. Indomethacin treatment and/or handling stress induced by simply measuring rectal temperature was found to dramatically alter the direction of the conditioned NK cell response. Conditioning of indomethacin treated mice produced a conditioned suppression of the NK cell response mimicking a conditioned tolerance response. If handling stress was superimposed on day 2 the conditioned suppression response was replaced by a conditioned augmentation of the NK cell response. Even with one trial conditioning, drugs and handling stress can serve as additional cues to alter the direction of the conditioned response. The studies also show that the conditioning of the fever response is independent of conditioning of the NK cell response.

Changes in the retrievability of associations to elements of the compound CS determine the expression of overshadowing

In two experiments, rats were presented with a taste conditioned stimulus (CS) alone, an odor CS alone, or an odor-taste compound followed by lithium chloride injection. When tested 1 day following conditioning, there was evidence that the odor cue overshadowed conditioning to the taste; however, there was no indication of following a longer (2I-day) retention interval, despite undiminished strength of the aversion in animals conditioned with only the single element (taste). The observed at the I-day retention interval was not reciprocal. Rats conditioned with the odor CS alone or with the compound CS expressed odor aversions of comparable strength-that is, no overshadowing. However, in contrast to the taste aversion, over­ shadowing of conditioning to the odor by taste was evident following a 2I-day retention interval. Rather than reflecting a failure of the overshadowed stimulus to acquire associative strength, these data suggest that may be expressed, or not expressed, as a result of changes in the relative retrievability of learned associations over time. When a compound conditioned stimulus (CS) made up of two separable elements (AB) is paired with an uncon­ ditioned stimulus (US), the conditioned responding elicited by the less salient element (B) is weaker than if it alone had been paired with the US. This overshadowing of B by A has been interpreted by major theories of Pav­ lovian conditioning as a failure of the overshadowed ele­ ment to be associated with the US (Mackintosh, 1975, 1976; Rescorla & Wagner, 1972). Recent evidence indi­ cates, however, that the overshadowed stimulus may in fact become associated with the US during conditioning and that represents a failure to express this learned association behaviorally. A variety of studies have reported that nonreinforced presentations of the stimulus following conditioning with a compound CS result in an enhanced level of conditioned responding to the overshadowed stimulus that may be comparable to the level observed to the more salient stimulus. This recovery from over­ shadowing, via extinction of the stimu­ lus, has been reported with either general activity (Kauf­ man & Bolles, 1981) or suppression of drinking (Matzel, Schachtman, & Miller, 1985; Matzel, Shuster, & Miller, 1987) as the index of conditioning. Recovery from has also been reported as a function of an increase in the retention interval be

Associative processes in early olfactory preference acquisition: Neural and behavioral consequences

Acquisition of behavioral conditioned responding and learned odor preferences during olfactory classical conditioning in rat pups requires forward or simultaneous pairings of the conditioned stimulus (CS) and the unconditioned stimulus (US). Other temporal relationships between the CS and US do not usually result in learning. The present study examined the influence of this CS-US relationship upon the neural olfactory bulb modifications that are acquired during early classical conditioning. Wistar rat pups were trained from Postnatal Days (PN) 1-18 with either forward (odor overlapping temporally with reinforcing stroking) or backward (stroking followed by odor) CS-US pairings. On PN 19, pups received either a behavioral odor preference test to the odor CS or an injection of (14)C 2-DG and exposure to the odor CS, or olfactory bulb single unit responses were recorded in response to exposure to the odor CS. Only pups that received forward presentations of the CS and US exhibited both a preference for the CS and modified olfactory bulb neural responses to the CS. These results, then, suggest that the modified olfactory bulb neural responses acquired during classical conditioning are guided by the same temporal constraints as those which govern the acquisition of behavioral conditioned responses.

Reinforcers in infancy: classical conditioning using stroking or intra-oral infusions of milk as UCS.

Six-day-old rats received 20 forward pairings of an odor-conditioned stimulus (CS) with one of two unconditioned stimuli (UCS); 1) intra-oral milk infusions or 2) stroking with a sable-hair brush. These UCS's produce a common general response of increased behavioral activity, but different specific behaviors. For each UCS, additional pups received backward pairings of the CS and UCS, random pairings of the CS and UCS, CS only, UCS only, or no stimuli. Four hours later, pups received a two-odor choice test to assess the development of an odor preference and a CS-only test to assess the acquisition of conditioned responding (CR). The results of the two-odor choice test indicated that for both UCS's only forward pairings of the CS and UCS resulted in an odor preference. Similarly, the CS-only test showed that only forward pairings of the CS and either UCS were effective in producing CR's; pups that received forward pairings exhibited increased behavioral activity during presentations of the CS, which is an unconditioned response (UCR) to both UCS's. Only the forward paired CS-milk UCS group exhibited increased mouthing and probing during the CS only test; these are UCR's that occur to milk infusions but infrequently to the stroking UCS. These results demonstrate the development of similar conditioned odor preferences using behaviorally activating UCS's, but CR's which are specific to the form of the UCR.

Disruption of neophobia, conditioned odor aversion, and conditioned taste aversion in rats with hippocampal lesions

Previous studies have implicated the hippocampus in the acquisition of conditioned taste aversions. However, the effect of hippocampal (HPC) lesions on the acquisition of conditioned aversions to the distal olfactory cue has not been investigated. In this study rats with bilateral electrolytic hippocampal lesions were given access to an odor conditioned stimulus (CS) alone or a compound odor-taste CS, followed by an injection of LiCl or saline. The results indicated that HPC lesions attenuated the neophobic response to both CSs, and disrupted conditioned odor and taste aversions, relative to sham-operated controls. Furthermore, the disruption in conditioned odor aversions could not be attributed to attenuation of neophobia in lesioned subjects nor to prolonged neophobia in sham-operated controls. The results are consistent with pharmacological studies in suggesting that the hippocampus is involved in the formation of conditioned odor aversions.