Single Neurons in the Dentate Gyrus and CA1 of the Hippocampus Exhibit Inverse Patterns of Encoding During Trace Fear Conditioning.

Trace fear conditioning is a hippocampus-dependent learning task that requires the association of an auditory conditioned stimulus (CS) and a shock unconditioned stimulus (US) that are separated by a 20-s trace interval. Single-neuron activity was recorded simultaneously from the dentate gyrus (DG) and CA1 of rats during unpaired pseudoconditioning and subsequent trace fear conditioning. Single neurons in DG showed a progressive increase in learning-related activity to the CS and US across trace fear conditioning. Single neurons in CA1 showed an early increase in responding to the CS, which developed into a decrease in firing later in trace conditioning. Correlation analyses showed that DG and CA1 units exhibit inverse patterns of responding to the CS during trace fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat

The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (1 5-s duration) followed by an empty 30-s trace interval and then a fear-producing floor-shock US (0.5-s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS-alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear-conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning.     

A model of hippocampal activity in trace conditioning: Where's the trace?

The hippocampus is generally thought to play a modulating role in the timing of conditioned responses in classical trace conditioning. One hypothesis is that the hippocampus stores a memory trace of the conditioned stimulus (CS) during the stimulus-free period. Cellular recordings, however, do not show any obvious CS storage. This article examines this issue by using a biologically plausible model of the CA3 region of the hippocampus. Simulations of the model reproduce both behavioral and physiological experimental data. On the basis of neural codes that develop in the model, the authors hypothesize that the hippocampus functions as a time-indexed encoding device for the CS and not as a CS storage buffer. Specifically, the CS initiates a sequence of neural activity during the trace interval that only indirectly represents the CS. The model yields 2 predictions: Some cells will increase in activity only during the trace interval, and some unconditioned stimulus (US)-coding cells will shift in time and fire before US onset. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning.

During Pavlovian fear conditioning a conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (UCS). In many studies the CS and UCS are paired on every trial, whereas in others the CS and UCS are paired intermittently. To better understand the influence of the CS-UCS pairing rate on brain activity, the experimenters presented continuously, intermittently, and non-paired CSs during fear conditioning. Amygdala, anterior cingulate, and fusiform gyrus activity increased linearly with the CS-UCS pairing rate. In contrast, insula and left dorsolateral prefrontal cortex responses were larger during intermittently paired CS presentations relative to continuously and non-paired CSs. These results demonstrate two distinct patterns of activity in disparate brain regions. Amygdala, anterior cingulate, and fusiform gyrus activity paralleled the CS-UCS pairing rate, whereas the insula and dorsolateral prefrontal cortex appeared to respond to the uncertainty inherent in intermittent CS-UCS pairing procedures. These findings may further clarify the role of these brain regions in Pavlovian fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Is Perruchet’s dissociation between eyeblink conditioned responding and outcome expectancy evidence for two learning systems?

P. Perruchet (1985b) showed a double dissociation of conditioned responses (CRs) and expectancy for an airpuff unconditioned stimulus (US) in a 50% partial reinforcement schedule in human eyeblink conditioning. In the Perruchet effect, participants show an increase in CRs and a concurrent decrease in expectancy for the airpuff across runs of reinforced trials; conversely, participants show a decrease in CRs and a concurrent increase in expectancy for the airpuff across runs of nonreinforced trials. Three eyeblink conditioning experiments investigated whether the linear trend in eyeblink CRs in the Perruchet effect is a result of changes in associative strength of the conditioned stimulus (CS), US sensitization, or learning the precise timing of the US. Experiments 1 and 2 demonstrated that the linear trend in eyeblink CRs is not the result of US sensitization. Experiment 3 showed that the linear trend in eyeblink CRs is present with both a fixed and a variable CS–US interval and so is not the result of learning the precise timing of the US. The results are difficult to reconcile with a single learning process model of associative learning in which expectancy mediates CRs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of training intertrial interval on acquisition of trace and long-delay fear conditioning in rats.

Many factors govern conditioning effectiveness, including the intertrial interval (ITI) used during training. The present study systematically varied the training ITI during both trace and long-delay fear conditioning. Rats were trained using one of six different ITIs and subsequently tested for conditioning to the white noise conditioned stimulus (CS) and the training context. After trace conditioning, percent freezing to the CS was positively correlated with training ITI, whereas percent freezing to the context was negatively correlated with training ITI. In contrast, when rats were trained using a long-delay paradigm, freezing during the CS test session did not vary as a function of training ITI; rats exhibited robust freezing at all ITIs. The long-delay conditioned rats exhibited relatively low levels of freezing during the context test. Thus, trace is more sensitive than long-delay fear conditioning to variations in the training ITI. These data suggest that training ITI is an important variable to consider when evaluating age or treatment effects, where the optimal ITI may vary with advancing age or pharmacological treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurophysiological theory of Kamin blocking in fear conditioning.

Kamin blocking in fear conditioning is thought to reflect diminished processing of the unconditional stimulus (US) in the presence of a conditional stimulus (CS+) that was previously paired with this US. According to Fanselow's (1998) hypothesis, the CS+ drives output from the amygdala that ultimately produces analgesia by causing opiate release onto afferent pain circuits. This hypothesis was explored quantitatively through neurophysiological simulations. The results suggest that opiate-mediated, negative-feedback control of US processing is too slow for efficient blocking of cue conditioning. The reason is that conditioning-produced synaptic modifications can be induced before the opiate-mediated inhibition has any substantial effect on US processing. The results suggest the existence of an additional, faster-acting, inhibitory neurotransmitter in the blocking circuit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid and robust olfactory conditioning with milk before suckling experience: Promotion of nipple attachment in the newborn rat.

An olfactory conditioning paradigm tested the hypothesis that newborn rats are able to learn about events associated with their first experience with milk as early as 3–5 hr after birth. Exposure to lemon odor (conditioned stimulus, [CS]) paired with intraoral milk infusions (unconditioned stimulus, [US]) resulted in strong conditioning: In the presence of the CS, sustained attachment occurred to an empty nipple as if it provided milk, whereas pups in control conditions showed little attachment. A single CS–US pairing was sufficient for strong conditioning, which was evident with a trace interval as long as 60 s. Conditioning was robust enough to promote attachment to a nipple providing saline, which is aversive to the newborn rat, and comparably strong conditioning occurred with sucrose or saccharin as the US. These findings suggest that olfactory conditioning has the potential to modify suckling behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Response rates track the history of reinforcement times.

When conditioning involves a consistent temporal relationship between the conditioned stimulus (CS) and unconditioned stimulus (US), the expression of conditioned responses within a trial peaks at the usual time of the US relative to the CS. Here we examine the temporal profile of responses during conditioning with variable CS–US intervals. We conditioned stimuli with either uniformly distributed or exponentially distributed random CS–US intervals. In the former case, the frequency of each CS–US interval within a specified range is uniform but the momentary probability of the US (the hazard function) increases as time elapses during the trial; with the latter distribution, short CS–US intervals are more frequent than longer intervals, but the momentary probability of the US is constant across time within the trial. We report that, in a magazine approach paradigm, rats' response rates remained stable as time elapses during the CS when the CS–US intervals were uniformly distributed, whereas their response rates declined when the CS–US intervals were exponentially distributed. In other words, the profile of responding during the CS matched the frequency distribution of the US times, not the momentary probability of the US during the CS. These results are inconsistent with real-time associative models, which predict that associative strength tracks the momentary probability of the US, but may provide support for timing models of conditioning in which conditioned responding is tied to remembered times of reinforcement. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Anterograde amnesia for Pavlovian fear conditioning and the role of one trial overshadowing: Effects of preconditioning exposures to morphine in rat.

Four experiments studied anterograde deficits in Pavlovian fear conditioning following prolonged exposure to the μ-opioid receptor agonist morphine. Injections of morphine produced temporally graded anterograde amnesia characterized by deficits in contextual and conditioned-stimulus (CS) conditioning 1 or 7 days and selective impairment in CS conditioning 21 days after last injection. This anterograde deficit in conditioning did not recover across a retention interval, was absent when rats were tested immediately after conditioning, and required the presence of an auditory CS. These results suggest that anterograde deficits in Pavlovian fear conditioning emerged from differences in susceptibility to 1-trial overshadowing of context by CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal processing of information: The role of the medial prefrontal cortex and hippocampus: Theoretical comment on gilmartin and mcechron (2005).

M. R. Gilmartin and M. D. McEchron (2005) reported that single cells recorded in the prelimbic cortex of rats during the acquisition of trace fear conditioning display multiple patterns of neuronal firing during the trace. These finding are discussed in the context of the role of the prelimbic cortex in processing temporal information during trace conditioning and delayed matching- or nonmatching-to-sample paradigms based on both electrophysiology and lesion evidence. In addition, evidence is provided for a role of the hippocampus in supporting temporal processing of information and its potential interaction with the prelimbic cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioid Receptors Regulate the Extinction of Pavlovian Fear Conditioning.

Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the development, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired trace and contextual fear conditioning in aged rats.

Trace and contextual fear conditioning were evaluated in adult (3-6 months), early middle-aged (8-12 months), late middle-aged (16-20 months), and aged (24-33 months) Sprague-Dawley rats. After trace conditioning, aged animals exhibited significantly less freezing to the tone conditioned stimulus and training context. Levels of trace-cue and context conditioning were negatively correlated with age (r = -0.56 and -0.59, respectively) and positively correlated with each other (r = +0.52). Aged rats showed robust conditioning in short- and long-delay fear paradigms, suggesting that the trace interval, rather than the use of a long interstimulus interval, is responsible for the aging-related deficits in trace fear conditioning. The authors suggest that these aging-related conditioning deficits furnish useful indices of functional changes within hippocampus or perirhinal cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian Conditioning: The CS-UR Relation.

A new Pavlovian procedure used fluid-elicited throat-movement responses of the pigeon (N=66) to study the effects on conditioning of the temporal relation of the conditioned stimulus (CS) to the unconditioned stimulus-unconditioned response (US-UR). Because the throat-movement response has a substantial latency and duration, the relation of the CS to the US and UR could be independently evaluated. Four experiments indicated that, operationally, the relation of the CS to the UR--not to the US--is critical for conditioning in this preparation. The conventional emphasis on CS-US relations is based on procedures that confound the occurrence of the US with the UR and that foster generalization decrement between training and testing. The authors indicate how several conditioning phenomena may be reinterpreted in terms of CS-UR relations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the Dorsal Hippocampus Block Trace Fear Conditioned Potentiation of Startle.

Several studies show that the hippocampus is critical for the memories mediating trace and contextual fear conditioning. This study investigates whether N-methyl-D-aspartate-induced lesions of the dorsal hippocampus made prior to training affect context fear conditioning and trace fear conditioning measured with the fear-potentiated startle. Pretraining excitotoxic lesions of the dorsal hippocampus blocked acquisition of trace fear conditioning to a tone stimulus but did not affect context fear conditioning. These data indicate that without a dorsal hippocampus rats are unable to acquire trace conditioning but can acquire contextual fear when fear is measured by potentiation of the startle response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Role for CS-US Contingency in Pavlovian Conditioning.

Two experiments evaluated the role of conditioned stimulus-unconditioned stimulus (CS-US) contingency in appetitive Pavlovian conditioning in rats. In both experiments, some groups received a positively contingent CS signaling an increased likelihood of the US relative to the absence of the CS. These groups were compared with control treatments in which the likelihood of the US was the same in the presence and absence of the CS. A trial marker served as a trial context. Experiment 1 found contingency sensitivity. There was a reciprocal relationship between responding to the CS and the trial marker. Experiment 2 showed that this result was not stimulus or response specific. These results are consistent with associative explanations and the idea that rats are sensitive to CS-US contingency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of forward or simultaneous conditioned stimulus-unconditioned stimulus intervals on the defensive behavior system of the Norway rat (Rattus norvegicus).

To test several predictions derived from a behavior-systems approach, the authors assessed Pavlovian fear conditioning in rats after 30 trials of forward, simultaneous, or unpaired training. Direct evidence of conditioned fear was collected through observation of flight and freezing reactions during presentations of the conditioned stimulus (CS) alone. The authors also tested the CS's potential to reinforce an instrumental escape response in an escape-from-fear paradigm. On the one hand, rats that received forward training showed conditioned freezing, but no conditioned flight was observed. On the other hand, rats that received simultaneous training showed conditioned flight, but no conditioned freezing was observed. Rats that received either forward or simultaneous pairings showed instrumental learning of the escape-from-fear response. Implications for several theories of Pavlovian conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Overshadowing and stimulus duration.

In 3 experiments, the authors investigated the effect of stimulus duration on overshadowing. Experiments 1 and 2 examined responding to a target conditioned stimulus (CS1) when it was conditioned in compound with a coterminating overshadowing stimulus (CS2) that was longer, shorter, or of the same duration (the long, short, and matched groups, respectively). Equal overshadowing of conditioning to CS1 was obtained in all 3 conditions relative to a control group conditioned to the light alone. There were, however, differences in responding to CS2 as a function of its absolute duration. Experiment 3 examined the contribution of the food-food interval/CS onset-food interval ratio to these findings. In Experiments 1 and 2, the ratio differed for the overshadowing CS but not for the target CS. In Experiment 3, this arrangement was reversed, but the pattern of results remained the same. The implications of these findings for trial-based and real-time models of conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sequence of single neuron changes in CA1 hippocampus of rabbits during acquisition of trace eyeblink conditioned responses

The sequence of changes in single neuron activity in the CA1 area of the rabbit hippocampus was examined during daily sessions (80 trials/session) of hippocampally dependent nonspatial trace eyeblink (i.e., nictitating membrane response) conditioning. Each trial for trace conditioned animals (n = 7) consisted of a tone conditioned stimulus (CS; 6 kHz; 90 dB, 100 ms) followed by a 500-ms silent trace period, then a corneal airpuff unconditioned stimulus (US; 3.0 psi; 150 ms). Control animals (n = 5) received unpaired CSs and USs. Most pyramidal (n = 309) and theta (n = 21) cells were recorded for a single day of training. The activity of cells for each animal were grouped according to: the day of training that CRs began to increase and the day of training that CR performance became asymptotic. Pyramidal cells from trace conditioned animals demonstrated several stages of learning-related activity: large increases in activity after both the CS and US early in conditioning on the day of training when CRs began to increase, smaller moderate increases in activity on the following days of training, and decreases in activity after the US during asymptotic CRs. Pyramidal cell-increases declined significantly across the trials of each daily session. Theta cells showed an activity pattern opposite to the pyramidal cells, consistent with the notion that theta cells have an inhibitory influence on pyramidal cells. Single pyramidal cells also were categorized into response profiles. Most pyramidal response profiles showed increases in activity specific to the day of initial CRs. Two of the pyramidal response profiles may be involved in assessing the temporal properties of the CS-US trace conditioning trial.     

Evaluative conditioning may incur attentional costs.

Evaluative conditioning (EC) refers to changes in the liking of an affectively neutral stimulus (conditioned stimulus, or CS) after pairing this stimulus with an affect-laden stimulus (unconditioned stimulus, or US). Several authors proposed that EC incurs little or no attentional cost. Using a rigorous design, we provide evidence that a reduction in attentional resources may have a negative impact on EC. Additional analyses also revealed that participants correctly encoded fewer CS–US pairings when their attentional resources were depleted. Replicating Pleyers, Corneille, Luminet, and Yzerbyt’s (2007) findings, EC was also obtained only for CSs that could be correctly linked to their associated US in the context of an identification task. This research clarifies the role of higher order processes in EC and has significant practical implications. (PsycINFO Database Record (c) 2010 APA, all rights reserved)