Conditioned Stimulus In Context Research Articles

Engram for the complex signals in the mouse brain: distinct neuronal ensembles for compound conditioning stimulus and its components

Natural learning involves multiple sensory modalities receiving complex stimuli. Elemental learning theories suggest separate encoding and association of each component in a compound signal. Configural theories predict the formation of a representation of the entire complex signal, which is associated with the second event. We developed a mouse model of fear conditioning to a compound tone-light cue or its separate components to test these alternative theories. First, we investigated the memory dynamics of compound cues and their individual components and discovered that they mature at varying times following conditioning. We demonstrated that the memory of the components matures at different intervals after training: memory of the auditory stimulus and the auditory component of CCS is demonstrated behaviorally right after training, whereas memory of the light stimulus and the light component of CCS matures within three days. The memory of CCS, its components, and discrete conditioned stimuli persists for an extended period, up to one month. A similar dissociation was observed in extinction experiments, revealing that the extinction of memory for one CCS component did not affect the memory of the other component when the extinction procedure began a day after training. In addition, when the extinction procedure began seven days after training, while the memory was fully mature, the extinction of one component of contextual conditional stimuli led to the extinction of the other component. Next, c-Fos imaging was conducted to examine cellular activity across multiple brain regions, including the frontal, prelimbic, cingulate, retrosplenial, parietal, primary and secondary visual, primary and secondary auditory cortices, as well as the hippocampus and amygdala. This examination was performed following conditioning using either the entire compound cue or its individual components. We discovered different cortical activation patterns between compound-cue and single-cue conditioning. Conditioning to the compound cue activated prelimbic and frontal associative cortices, whereas single cues did not. Third, we demonstrated that retrieval of memory only through the entire compound cue, and not through single cues, activated the parietal cortex, primary visual cortex, mediolateral secondary visual cortices, and hippocampal CA1. Fourth, through in vivo two-photon imaging, we examined retrieval-induced c-Fos expression in the parietal cortex of fos-EGFP transgenic mice and identified at least three distinct neuronal populations with differential response specificity to the compound signal and its components. Taken together, our data suggest that intricate signals have the potential to establish both integral and elemental neuronal representations. These representations can be used separately in behavior and have different long-term memory dynamics.

Temporal association activates projections from the perirhinal cortex and ventral CA1 to the prelimbic cortex and from the prelimbic cortex to the basolateral amygdala.

In trace fear conditioning, the prelimbic cortex exhibits persistent activity during the interval between the conditioned and unconditioned stimuli, which maintains a conditioned stimulus representation. Regions cooperating for this function or encoding the conditioned stimulus before the interval could send inputs to the prelimbic cortex, supporting learning. The basolateral amygdala has conditioned stimulus- and unconditioned stimulus-responsive neurons, convergently activated. The prelimbic cortex could directly project to the basolateral amygdala to associate the transient memory of the conditioned stimulus with the unconditioned stimulus. We investigated the neuronal circuit supporting temporal associations using contextual fear conditioning with a 5-s interval, in which 5s separates the contextual conditioned stimulus from the unconditioned stimulus. Injecting retrobeads, we quantified c-Fos in prelimbic cortex- or basolateral amygdala-projecting neurons from 9 regions after contextual fear conditioning with a 5-s interval or contextual fear conditioning, in which the conditioned and unconditioned stimuli overlap. The contextual fear conditioning with a 5-s interval activated ventral CA1 and perirhinal cortex neurons projecting to the prelimbic cortex and prelimbic cortex neurons projecting to basolateral amygdala. Both fear conditioning activated ventral CA1 and lateral entorhinal cortex neurons projecting to basolateral amygdala and basolateral amygdala neurons projecting to prelimbic cortex. The perirhinal cortex→prelimbic cortex and ventral CA1→prelimbic cortex connections are the first identified prelimbic cortex afferent projections participating in temporal associations. These results help to understand time-linked memories, a process required in episodic and working memories.

Modulation of object memory consolidation by heroin and heroin-conditioned stimuli: Role of opioid and noradrenergic systems

There is recent evidence that cocaine, nicotine, and their conditioned stimuli have the ability to enhance memory consolidation. The present study compared the effects of post-training heroin and of a heroin contextual conditioned stimulus (CS+) on consolidation of object recognition memory and investigated the roles of opioid and beta-adrenergic receptors in heroin/CS+ memory modulation by co-administering the respective antagonists, naltrexone (NTX) and propranolol (PRO). Three experiments were performed in male Sprague-Dawley rats demonstrating that immediate, but not delayed, post-sample exposure to heroin (0.3, 1 mg/kg), or exposure (30 min) to a contextual CS+ paired with 1 mg/kg heroin (5 pairings, each 120 min), equally enhanced object memory. Importantly, while the memory enhancing effects of 1 mg/kg heroin and of the contextual CS+ were not altered by post-training co-administration of 3 mg/kg naltrexone, they were blocked by post-training co-administration of 10 mg/kg propranolol. Taken together, these data suggest that a context paired with heroin shares the memory enhancing effect of heroin itself and that these unconditioned and conditioned drug stimuli may modulate memory through the activation of beta-noradrenergic receptors.

Alarm pheromone does not modulate 22-kHz calls in male rats

Rats are known to emit a series of ultrasonic vocalizations, termed 22-kHz calls, when exposed to distressing stimuli. Pharmacological studies have indicated that anxiety mediates 22-kHz calls in distressed rats. We previously found that exposure to the rat alarm pheromone increases anxiety in rats. Therefore, we hypothesized that the alarm pheromone would increase 22-kHz calls in pheromone-exposed rats. Accordingly, we tested whether exposure to the alarm pheromone induced 22-kHz calls, as well as whether the alarm pheromone increased 22-kHz calls in response to an aversive conditioned stimulus (CS). Rats were first fear-conditioned to an auditory and contextual CS. On the following day, the rats were either exposed to the alarm pheromone or a control odor that was released from the neck region of odor-donor rats. Then, the rats were re-exposed to the aversive CS. The alarm pheromone neither induced 22-kHz calls nor increased 22-kHz calls in response to the aversive CS. In contrast, the control odor unexpectedly reduced the total number and duration of 22-kHz calls elicited by the aversive CS, as well as the duration of freezing. These results suggest that the alarm pheromone does not affect 22-kHz calls in rats. However, we may have found evidence for an appeasing olfactory signal, released from the neck region of odor-donor rats.

The 3-second auditory conditioned stimulus is a more effective stressor than the 20-second auditory conditioned stimulus in male rats

Using fear-conditioning model, we have used a 3-s auditory conditioned stimulus (CS) as a stressor and observed fear and stress responses during a specific experimental period regardless of the presence or absence of the CS. Because the CS was extremely short compared with the experimental period, we observed responses primarily in the absence of the CS. In contrast, most studies in the literature have analyzed responses in the presence of the CS. Therefore, the characteristics of fear and stress responses in the absence of the CS remain to be clarified. To clarify this, we compared the characteristics of fear and stress responses elicited by a 3-s auditory CS with those observed during a 20-s auditory CS. The basolateral complex of the amygdala (BLA), but not the bed nucleus of the stria terminalis (BNST), participated in the fear response elicited by the 3-s CS, whereas both the BLA and BNST were involved in the response observed during the 20-s CS. Additional analyses revealed that the BNST participated in the fear response during the 20-s CS when the CS was paired with a 0.75-mA, but not with a 0.9-mA, foot shock, and to the contextual CS. In addition, the fear response elicited by the 3-s CS was more resistant to extinction than that during the 20-s CS. Finally, the 3-s CS produced more intense freezing and corticosterone secretion than the 20-s CS. On the basis of these characteristics, we conclude that the 3-s auditory CS is a more effective stressor than the 20-s auditory CS. Our findings also suggest that foot shock intensity is an additional determinant in the type of fear response induced by the CS.

Dual-Tasking Attenuates the Return of Fear after Extinction

Return of fear following exposure treatment may be explained by ABA-renewal: fear acquired in context A, and extinguished in context B, may return in context A. Conditioning theory predicts that intensity of conditioned fear is mediated by the mental representation of the unconditioned stimulus (US) evoked by the conditioned stimulus (CS). This study tested whether US-devaluation via a dual-task – imagining the US while making eye movements – attenuates fear renewal. Participants acquired fear in context A, and underwent extinction in context A or B. Next, two groups did a filler task (AAA; ABA), one a dual-task of US imagination with eye movements (ABA-DT), and one merely imagined the US (ABA-RO). Finally, participants were re-presented the CSs in context A. ABA-renewal was found for US-expectancy. Dual-tasking, but not recall only, reduced fear renewal. No between-group differences were observed in reductions of vividness, emotionality, and startle responses to the US. Findings suggest that dual-tasking may attenuate fear renewal.

Contextual fear cues inhibit eating in food-deprived male and female rats

Previously we have shown that food-deprived male and female rats inhibit food consumption when presented with a discrete conditioned stimulus that signals danger. Here, in a series of three experiments, we examined whether contextual conditioned stimuli can exert the same effect. Experiment 1 paired a distinct context with footshocks, to examine food intake in food-deprived rats upon re-exposure to the context. Experiment 2 used a discrimination protocol with two alternating contexts; rats were given food in one, and received footshocks in the other. This protocol allowed us to monitor food consumption during training in a context never associated with footshocks, and to evaluate consumption at test in a context that had been previously paired with footshocks. Experiments 1 and 2 compared experimental groups to controls that never received footshocks. Experiment 3 used a within-subjects design to assess the specificity of the inhibition by the contextual cues, separate from any generalized effects due solely to the prior experience of footshocks. Our results demonstrate that similar to discrete cues, contextual cues previously associated with aversive events can inhibit feeding in food-deprived animals. These findings are important for our understanding of environmental contributions to the control of food intake.

18-Methoxycoronaridine blocks context-induced reinstatement following cocaine self-administration in rats

Numerous studies utilizing drug self-administration have shown the importance of conditioned cues in maintaining and reinstating addictive behaviors. However, most used simple cues that fail to replicate the complexity of cues present in human craving and addiction. We have recently shown that music can induce behavioral and neurochemical changes in rats following classical conditioning with psychostimulants. However, such effects have yet to be characterized utilizing operant self-administration procedures, particularly with regard to craving and relapse. The goal of the present study was to validate the effectiveness of music as a contextual conditioned stimulus using cocaine in an operant reinstatement model of relapse. Rats were trained to lever press for cocaine with a musical cue, and were subsequently tested during reinstatement sessions to determine how musical conditioning affected drug seeking behavior. Additionally, in vivo microdialysis was used to determine basolateral amygdala involvement during reinstatement. Lastly, tests were conducted to determine whether the putative anti-addictive agent 18-methoxycoronaridine (18-MC) could attenuate cue-induced drug seeking behavior. Our results show that music-conditioned animals exhibited increased drug seeking behaviors when compared to controls during reinstatement test sessions. Furthermore, music-conditioned subjects exhibited increased extracellular dopamine in the basolateral amygdala during reinstatement sessions. Perhaps most importantly, 18-MC blocked musical cue-induced reinstatement. Thus, music can be a powerful contextual conditioned cue in rats, capable of inducing changes in both brain neurochemistry and drug seeking behavior during abstinence. The fact that 18-MC blocked cue-induced reinstatement suggests that α3β4 nicotinic receptors may be involved in the mechanism of craving, and that 18-MC may help prevent relapse to drug addiction in humans.

Music-induced context preference following cocaine conditioning in rats.

Traditional models of drug-seeking behavior have shown that exposure to associated environmental cues can trigger relapse. These learned associations take place during repeated drug administration, resulting in conditioned reinforcement. Although considerable investigation has occurred regarding simple conditioned stimuli, less is known about complex environmental cues, particularly those that may be salient in human addiction. Recent studies indicate that music can serve as a contextual conditioned stimulus in rats and influence drug-seeking behavior during abstinence. The purpose of the present study was to further assess the effectiveness of music as a conditioned stimulus in rats, to determine rats' preferences for two contrasting pieces of music, and to determine rats' preferences for music versus silence. To this end, we created an apparatus that gave instrumental control of musical choice (Miles Davis vs. Beethoven) to the rats themselves. After determining baseline musical preference, animals were conditioned with cocaine (10 mg/kg) to the music they initially preferred least, with alternating conditioning sessions pairing saline with the music preferred most. The animals were subsequently tested in a drug-free state to determine what effect this conditioning had on musical preference. The results indicate that music serves as an effective contextual conditioned stimulus, significantly increasing both musical preference and locomotor activity after repeated cocaine conditioning. Furthermore, we found that rats initially favor silence over music, but that this preference can be altered as a result of cocaine-paired conditioning. These findings demonstrate that, after repeated association with reward (cocaine), music can engender a conditioned context preference in rats; these findings are consistent with other evidence showing that musical contextual cues can reinstate drug-seeking behavior in rats.

Music and methamphetamine: Conditioned cue-induced increases in locomotor activity and dopamine release in rats

Associations between drugs of abuse and cues facilitate the acquisition and maintenance of addictive behaviors. Although significant research has been done to elucidate the role that simple discriminative or discrete conditioned stimuli (e.g., a tone or a light) play in addiction, less is known about complex environmental cues. The purpose of the present study was to examine the role of a musical conditioned stimulus by assessing locomotor activity and in vivo microdialysis. Two groups of rats were given non-contingent injections of methamphetamine (1.0mg/kg) or vehicle and placed in standard conditioning chambers. During these conditioning sessions both groups were exposed to a continuous conditioned stimulus, in the form of a musical selection (“Four” by Miles Davis) played repeatedly for 90min. After seven consecutive conditioning days subjects were given one day of rest, and subsequently tested for locomotor activity or dopamine release in the absence of drugs while the musical conditioned stimulus was continually present. The brain regions examined included the basolateral amygdala, nucleus accumbens, and prefrontal cortex. The results show that music is an effective contextual conditioned stimulus, significantly increasing locomotor activity after repeated association with methamphetamine. Furthermore, this musical conditioned stimulus significantly increased extracellular dopamine levels in the basolateral amygdala and nucleus accumbens. These findings support other evidence showing the importance of these brain regions in conditioned learning paradigms, and demonstrate that music is an effective conditioned stimulus warranting further investigation.

The exclusive induction of extinction is gated by BDNF

We have previously reported that the reconsolidation and extinction of hippocampal-dependent contextual fear memory can be initiated by a single context conditioned stimulus (CS) presentation of either short or long duration, and that both processes require protein synthesis in this brain region. Furthermore, reconsolidation depends on Zif268 activity in this region. Here we show that by infusing a recombinant brain-derived neurotrophic factor (rBDNF) directly into the brain of rats, that high levels of mature BDNF in the hippocampus at retrieval constrain the extinction of the fear memory after prolonged memory recall. We also show after a short CS exposure that reconsolidation was impaired using antisense oligonucleotides targeting Zif268, and that, similarly, reductions in conditioned behavior were observed after prolonged CS presentation when extinction is constrained by high levels of BDNF. This is direct evidence that in the mammalian brain extinction proceeds exclusively after prolonged CS exposure. In addition, that BDNF activity in the hippocampus contributes to a molecular switch for the extinction of hippocampal-dependent memory.

Involvement of Different Types of Dopamine Receptors in the Formation of Latent Inhibition of a Conditioned Passive Avoidance Reaction in Rats

The effects of systemic injections of dopaminergic agents on normal and weak latent inhibition of a conditioned passive avoidance reaction were studied in rats. Formation of normal latent inhibition was induced using 20 pre-exposures to a contextual conditioned stimulus prior to training. Weak latent inhibition was modeled using 10 pre-exposures. The effects of the D(2)/D(3) receptor agonist quinpirole (1 mg/kg) and the D(1) receptor agonist SKF 38393 (1 mg/kg) separately and in combination with haloperidol (0.5 mg/kg) were tested. Quinpirole induced the expression of normal latent inhibition but had no effect on weak latent inhibition. Activation of D(1) receptors with SKF 38393 had no effect on the formation of latent inhibition regardless of the number of pre-exposures. Haloperidol significantly strengthened weak latent inhibition but impaired normal latent inhibition. Administration of haloperidol in combination with SKF 38393 prevented this impairment. These results suggest that while D(1) receptors have no influence as an independent substrate on the formation of latent inhibition, activation of these receptors is required for the complete manifestation of D(2)-mediated modulation of this process.

Medial Prefrontal Cortex Is Necessary for an Appetitive Contextual Conditioned Stimulus to Promote Eating in Sated Rats

Motivation plays an important role in the control of food intake. A cue that acquires motivational properties through pairings with food consumption when an animal is hungry can override satiety and promote eating in sated rats. This phenomenon of conditioned potentiation of feeding is mediated by connections between the forebrain and the lateral hypothalamic area (LHA). In a recent study using markers for cellular activation, neurons in the ventral medial prefrontal cortex (vmPFC) that project directly to the LHA were strongly engaged after exposure to a conditioned cue that stimulates eating in sated rats. Here, we examined whether those vmPFC neurons are necessary for conditioned potentiation of eating. We trained rats in a paradigm in which the context provided conditioning cues. Rats with bilateral neurotoxic lesions of vmPFC were impaired in context-enhanced food consumption in tests when the rats were sated. At the same time, vmPFC lesions did not produce changes in food consumption in the home cage or changes in body weight during training. Thus, vmPFC neurotoxic lesions produced impairment in food consumption specifically driven by conditioned motivational cues. The current findings suggest a critical role for vmPFC in the brain network that mediates control of conditioned motivation to eat perhaps by a mechanism akin to appetite or craving.

Learned contextual cue potentiates eating in rats

Explicit cues associated with food consumption when hunger prevails will enhance eating when they are subsequently presented under conditions of satiety. Here we examined whether contextual conditioned stimuli (CSs) paired with consumption of food pellets while rats were food-deprived would enhance consumption of this food in rats that were not food-deprived. The conditioning context enhanced rats' consumption of the training food, but it did not change their consumption of the familiar, lab chow. These results show that the contextual CSs, like discrete cues, could modulate food consumption in a CS-potentiated eating paradigm. Furthermore, the data suggest that CS-potentiation of eating does not induce a general motivation to eat, akin to hunger, but instead more likely produces a more specific motivational state, akin to craving.

Glutamate receptor antagonist infusions into the basolateral and medial amygdala reveal differential contributions to olfactory vs. context fear conditioning and expression

The basolateral amygdala's involvement in fear acquisition and expression to visual and auditory stimuli is well known. The involvement of the basolateral and other amygdala areas in fear acquisition and expression to stimuli of other modalities is less certain. We evaluated the contribution of the basolateral and medial amygdala to olfactory and to context fear and fear conditioning by infusing into these areas the NMDA receptor antagonist AP5, the AMPA/kainate receptor antagonist NBQX, or vehicle prior to either odor-shock pairings or fear-potentiated startle testing. Pre-training AP5 infusions into the basolateral amygdala disrupted fear conditioning to the odor but not the context conditioned stimulus (CS). Pre-test NBQX infusions disrupted fear-potentiated startle to the odor but not context CS. Neither compound blocked fear conditioning when infused into the medial amygdala prior to training, but pre-test NBQX infusions did block fear-potentiated startle. The results confirm and extend recent findings suggesting a role for the basolateral amygdala in olfactory fear and fear conditioning, reveal an unexpected dissociation of the basolateral amygdala's involvement in discrete cue versus context fear and fear conditioning, and implicate for the first time the medial amygdala in fear-potentiated startle.

Brain-derived neurotrophic factor plays a critical role in contextual fear conditioning.

In this study, brain-derived neurotrophic factor (BDNF) heterozygous knock-outs were tested on fear conditioning, and their wild-type littermates were used as controls. Results showed that BDNF(+/-) mice are impaired in contextual learning, whereas tone learning remains intact. Because BDNF is involved in synaptic transmission and contextual learning is hippocampal dependent, we hypothesized that this deficit is attributable to abnormal BDNF-modulated synaptic plasticity in the hippocampus. A "gain-of-function" experiment was performed next by infusing recombinant BDNF protein into the hippocampal formation to investigate whether this deficit can be rescued. Infusion of BDNF protein into the hippocampus appeared to partially restore contextual fear learning of BDNF(+/-) mice. In conclusion, the present study suggests that BDNF plays a critical role in fear conditioning. Loss of one copy of the BDNF gene leads to impairment of contextual fear learning in BDNF(+/-). This deficit can be partially rescued by infusing BDNF protein into the hippocampus. Other brain regions interacting with the hippocampus in the context conditioned stimulus pathway, for example, the amygdala, may also require normal BDNF expression levels to fully rescue this impairment.

Consolidation of CS and US representations in associative fear conditioning.

Much attention has been paid to the associative processes that are necessary to fuse together representations of the various components of an episodic memory. In the present study, we focus on the processes involved in the formation of lasting representations of the individual components that make up a fear-conditioning episode. In one-trial contextual fear conditioning experiments, weak conditioning to context occurs if the shock is delivered immediately following placement of the animal in a novel conditioning apparatus, a phenomenon known as the immediate shock deficit. We show that the immediate shock deficit in mice may be alleviated by pre-exposure to either the context or shock. In using this approach to temporally dissect a contextual fear-conditioning task into its constituent representational and associative processes, we are able to examine directly the processes that are important for formation of lasting representations of the context conditioned stimulus (CS) or unconditioned stimulus (US). Our data indicate that the formation of a lasting representation of the context or shock engages protein synthesis-dependent processes. Furthermore, genetic disruption of cAMP-responsive element binding protein (CREB), a transcription factor that regulates the synthesis of new proteins required for long-term memory, disrupts the formation of lasting context memories. We go on to show that the stress hormone epinephrine modulates the consolidation of a context memory, and reverses consolidation deficits in the CREB-deficient mice. Finally we show that disrupting either NMDA or calcium/calmodulin-dependent kinase II (CaMKII) function impairs consolidation of context memories. Together, these data suggest that this approach is particularly suited for the characterization of molecular and cellular processes underlying the formation of stimulus representations.

Selective responding of nucleus accumbens core and shell dopamine to aversively conditioned contextual and discrete stimuli

Dopamine transmission within the nucleus accumbens has been implicated as a neurochemical substrate of associative learning processes. It has been suggested that the acquisition of classically conditioned fear to a specific environment, or context, differs fundamentally from the development of conditioned fear to a discrete stimulus, such as a light or a tone. In this study, we assessed extracellular dopamine in the rat nucleus accumbens shell and core during the expression of a conditioned fear response. Animals were aversively conditioned to either a context or a tone and extracellular dopamine was measured in the nucleus accumbens shell and core by in vivo microdialysis over the next 2 days as animals were returned first to the conditioning chamber (day 1: context test), and subsequently as animals were again returned to the chamber and presented with the conditioned tone stimulus (day 2: tone test). Dopamine levels in the core were significantly higher in the Context-Shock group compared to the Tone-Shock group during the 30-min exposure to context while dopamine levels in the nucleus accumbens shell did not differ significantly during the context test between groups. In contrast, extracellular dopamine in the shell but not the core of Tone-Shock animals increased significantly during presentation of the tone. Dopamine in both the shell and core remained unchanged during the tone test in the Context-Shock groups. These data suggest distinct roles for shell and core dopamine transmission in the expression of a conditioned emotional response. While dopamine increased in the shell primarily during the presentation of a discrete tone conditioned stimulus, core dopamine responded more to a contextual conditioned stimulus. These results may reflect differences in either the type of information acquired or the salience of the learned associations which are formed to a context vs. a discrete tone cue.

Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats.

A large body of literature implicates the amygdala in Pavlovian fear conditioning. In this study, we examined the contribution of individual amygdaloid nuclei to contextual and auditory fear conditioning in rats. Prior to fear conditioning, rats received a large electrolytic lesion of the amygdala in one hemisphere, and a nucleus-specific neurotoxic lesion in the contralateral hemisphere. Neurotoxic lesions targeted either the lateral nucleus (LA), basolateral and basomedial nuclei (basal nuclei), or central nucleus (CE) of the amygdala. LA and CE lesions attenuated freezing to both contextual and auditory conditional stimuli (CSs). Lesions of the basal nuclei produced deficits in contextual and auditory fear conditioning only when the damage extended into the anterior divisions of the basal nuclei; damage limited to the posterior divisions of the basal nuclei did not significantly impair conditioning to either auditory or contextual CS. These effects were typically not lateralized, although neurotoxic lesions of the posterior divisions of the basal nuclei had greater effects on contextual fear conditioning when the contralateral electrolytic lesion was placed in the right hemisphere. These results indicate that there is significant overlap within the amygdala in the neural pathways mediating fear conditioning to contextual and acoustic CS, and that these forms of learning are not anatomically dissociable at the level of amygdaloid nuclei.

Contextual control of appetitive conditioning: influence of a contextual stimulus generated by a partial reinforcement procedure.

Three experiments with rat subjects examined the effects of a context switch after conditioning treatments in which the conditioned stimulus (CS) was either paired with food on every presentation (continuous reinforcement) or on some of its presentations (partial reinforcement). In each experiment, a target CS was given one of these treatments in Context A, and another CS was given a treatment during sessions that were intermixed in Context B. Final tests of the target CS in Context A and Context B often revealed no loss of responding with the switch to B. However, a loss was observed when partial reinforcement had been associated with Context A and continuous reinforcement had been associated with Context B. Those conditions caused equal decrements in responding to partially reinforced and continuously reinforced targets. The results suggest that under the present conditions partial reinforcement can generate a contextual stimulus that becomes associated with the physical context and controls responding to the CS.