Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats.

Water-deprived and nondeprived rats were fear conditioned with a discrete tone CS and an aversive footshock unconditioned stimulus/stimuli (UCS). 24 and 48 hrs following conditioning, conditional fear to the tone CS and the context cues of the conditioning chamber, respectively, were assessed by measuring freezing behavior. Water deprivation had no effect on baseline responding to either tone or contextual stimuli. Following either 1 or 3 tone-shock pairings, however, water deprivation selectively enhanced conditional freezing to the contextual cues of the training chamber; conditional freezing to the tone was unaffected by water deprivation. These results are consistent with the view that water deprivation affects fear conditioning via an influence on the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fischer 344 Rats Display Age-Related Memory Deficits in Trace Fear Conditioning.

A functional hippocampus is required for trace fear conditioning, which involves learning the association of a tone and shock that are separated over time. Young and aged rats received 10 trace conditioning trials. Twenty-four hours later, rats were tested for fear to the tone in a novel chamber by measuring freezing. The results showed significantly lower levels of freezing in aged rats as compared with young rats, which provides evidence of age-related memory impairments. Pseudorandom conditioning groups showed low levels of freezing, indicative of no associative memory. Age-related memory deficits were not found with delay conditioning, which suggests no age-related sensory-motor deficits. These data suggest that aging hinders the ability of the hippocampus to process information separated over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of contextual conditioning by the median raphe nucleus

The median raphe nucleus (MRN) has been suggested as the origin of a behavioral inhibition system that projects to the septum and hippocampus. Electrical stimulation of this mesencephalic area causes behavioral and autonomic manifestations characteristic of fear such as, freezing, defecation and micturition. In this study we extend these observations by analyzing the behavioral and autonomic responses of rats with lesions in the MRN submitted to a contextual conditioning paradigm. The animals underwent electrolytic or sham lesions of the median raphe nucleus. One day (acute) or 7 days (chronic) later they were tested in an experimental chamber where they received 10 foot-shocks (0.7 mA, 1 s with 20-s interval). The next day, sham and MRN-lesioned animals were tested again either in the same or in a different experimental chamber. During this, the duration of freezing, rearings, bouts of micturition and number of fecal boli were recorded. Sham-operated rats placed in the same chamber showed more freezing than rats exposed to a different context. This freezing behavior was clearly suppressed in rats with acute or chronic lesions in the MRN. MRN lesions also reduced the bouts of micturition and number of fecal boli. These rats showed a reduced number of rearings than sham-lesioned rats. This effect is probably the result of the displacement effect provoked by freezing since no significant differences in the number of rearings could be observed between these animals and the NMR-lesioned rats tested in an open field. This lesion produced higher horizontal locomotor activity in this test than the controls (sham-lesioned rats). These results point to the importance of the median raphe nucleus in the processing of fear conditioning with freezing being the most salient feature of it. Behavioral inhibition is also under control of MRN but its neural substrate seems to be dissociated from that of contextual fear.     

Selective impairment of long-term but not short-term conditional fear by the N-methyl-D-aspartate antagonist APV.

Previous research has indicated that the competitive N-methyl-D-aspartate (NMDA) antagonist APV ({dl}-2-amino-5-phosphonovalerate) prevents the Pavlovian conditioning of fear to contextual stimuli when tested 24 hrs, but not immediately, after training. The present study investigated this differential time-dependent effect of APV on fear conditioning. Rats were given either APV or saline and presented with 3 footshocks in a distinctive chamber. Promptly after the shock, rats that had received APV exhibited a species-typical fear response: freezing. However, the freezing lasted for only a short period of time (     

Disruptive effects of posttraining perirhinal cortex lesions on conditioned fear: Contributions of contextual cues.

Lesions placed in the rostral perirhinal cortex (rPRh) after fear conditioning interfere with the expression of conditioned fear responses elicited by auditory and visual conditioned stimuli when these stimuli are presented in a context that differs from the conditioning context. The present study examined whether lesions of the rPRh have similar effects when animals are tested in the conditioning context. Two days after male rats received classical fear conditioning, involving the pairing of an auditory CS with footshock, bilateral electrolytic lesions were produced in the rPRh. Five days later conditioned freezing behavior was measured during a 60-s exposure to the CS in a novel context and then 1 hr later in the conditioning context. There were 3 major findings: rPRh-lesioned Ss froze significantly less than controls to the CS in the novel context, thus confirming previously reported findings. rPRh-lesioned Ss also froze less than controls to the CS in the conditioning context, but froze significantly more to the CS in the conditioning than in the novel context, suggesting that at least part of the deficit in the novel context is due to the absence of contextual cues. Ss with rPRh lesions froze significantly less than controls to the conditioning context itself.… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Exercise on Pavlovian Fear Conditioning.

Exercise promotes multiple changes in hippocampal morphology and should, as a result, alter behavioral function. The present experiment investigated the effect of exercise on learning using contextual and auditory Pavlovian fear conditioning. Rats remained inactive or voluntarily exercised (VX) for 30 days, after which they received auditory-cued fear conditioning. Twenty-four hours later, rats were tested for learning of the contextual and auditory conditional responses. No differences in freezing behavior to the discrete auditory cue were observed during the training or testing sessions. However, VX rats did freeze significantly more compared to controls when tested in the training context 24 hr after exposure to shock. The enhancement of contextual fear conditioning provides further evidence that exercise alters hippocampal function and learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences, context preexposure, and the immediate shock deficit in Pavlovian context conditioning with mice.

The acquisition of context fear in rats is affected by variables such as the sex of the animal, the placement to shock interval (PSI), and preexposure to the context. The current experiments assessed the effects of these variables on context conditioning in mice (C57BL/6). In Experiment 1, mice were placed in a chamber and received a single shock 5 s, 20 s, 40 s, 60 s, 180 s, or 720 s later. Increasing the PSI produced corresponding increases in conditional freezing during the context test. In addition, male mice acquired more context conditioning than female mice did but only at intermediate PSIs. In Experiment 2, preexposure to the context before training alleviated the sex difference found with an intermediate PSI. The results are discussed in terms of configural learning theory and are argued to be contrary to the predictions of scalar expectancy theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotoxic or electrolytic lesions of the ventral subiculum produce deficits in the acquisition and expression of Pavlovian fear conditioning in rats.

The effects of neurotoxic or electrolytic ventral subicular (vSUB) lesions on the acquisition and expression of Pavlovian fear conditioning in rats were examined. Conditioning consisted of the delivery of tone–footshock trials in a novel observation chamber, and freezing served as the measure of conditional fear. Pretraining vSUB lesions produced a severe tone freezing deficit and a modest context freezing deficit, whereas posttraining lesions produced severe deficits in freezing to both a tone -and a context conditional stimulus (CS). Similar impairments were produced by neurotoxic and electrolytic lesions. Increases in motor activity associated with the lesions could not account for freezing deficits. These results reveal that neurons in the vSUB have an important role in both the acquisition and expression of Pavlovian fear conditioning to contextual and acoustic CSs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lesions to the hippocampus on contextual fear: Evidence for a disruption of freezing and avoidance behavior but not context conditioning.

The effects of ibotenic lesions of the hippocampus on conditioning to contextual cues during classical fear conditioning in rats were evaluated by (a) the amount of freezing elicited by contextual cues and (b) the relative avoidance of a shock compartment. In Experiment 1, lesions to the hippocampus had no effect on contextual freezing and marginally affected avoidance after repeated sessions. Experiment 2 showed that lesions to the hippocampus disrupted avoidance when tested after a single conditioning session, while leaving unaffected the acquisition of contextual freezing. Experiment 3 indicated that these lesions decreased the acquisition of contextual freezing when higher footshock intensity was used but had no effect on avoidance after repeated conditioning sessions. These results show that freezing and avoidance do not quantify context conditioning similarly. They further indicate that lesions to the hippocampus may disrupt the expression of these behaviors used as measures of context conditioning but not the acquisition of context conditioning per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial exploration is required for the formation of contextual fear memory.

The acquisition of contextual fear in mice is thought to require the formation of a conjunctive representation of the conditioning chamber. This can be achieved during a minimum of 20 to 40 s of exploration immediately prior to the shock or during preexposure to the context at an earlier time. An animal receiving less time in the chamber will show reduced freezing 24 hr later, a condition termed the immediate shock deficit (ISD). In this study, the authors have attempted to uncouple the formation of a contextual representation, based on the conjunction of a defined set of cues, from the establishment of a spatial representation, which requires active exploration, by inserting a transparent plastic partition in the center of the chamber. Taking advantage of the ISD and the context preexposure effect, the authors found that animals preexposed to one side of the chamber on Day 1, but shocked on the other side on Day 2, show significantly less fear than animals exposed to and shocked on the same side. Our results indicate that spatial exploration is necessary for mice to benefit from contextual preexposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recent Exposure to a Dangerous Context Impairs Extinction and Reinstates Lost Fear Reactions.

Rats were shocked in a context and then exposed to that context in the absence of shock. Shorter intervals between these extinction trials produced more long-term freezing than did longer ones, and shorter intervals between the final extinction trial and test produced more freezing than did longer ones. A short interval between a context extinction trial and test with an extinguished conditioned stimulus (CS) produced more freezing than did a longer one, and a short interval between a nonreinforced context exposure and an extinguished CS reinstated freezing when the CS was tested 24 hr later. The results suggest that recent fear acts to favor subsequent retrieval of the memory formed at conditioning rather than extinction and to render the retrieved memory more salient. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dorsal hippocampus involvement in trace fear conditioning with long, but not short, trace intervals in mice.

Placing a "trace" interval between a warning signal and an aversive shock makes consolidation of the memory for trace conditioning hippocampus dependent. To determine the trace at which memory consolidation requires the hippocampus, mice were trained with 0-s, 1-s, 3-s, or 20-s trace intervals and tested for freezing to context and tone. Posttraining dorsal hippocampus (DH) lesions decreased context conditioning regardless of trace interval. However, DH lesions attenuated only the 20-s trace tone freezing. Like eyeblink conditioning, the DH is necessary for trace fear conditioning only at long trace intervals, but the time scale for the effective interval in fear conditioning is about 40 times longer. Manipulations that alter trace fear conditioning with short trace intervals probably do not reflect altered DH function. Given this difference in time scale along with the use of posttraining DH lesions, hippocampus dependency of trace conditioning is not related to a bridging function or response timing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A short intertrial interval facilitates acquisition of context-conditioned fear and a short retention interval facilitates its expression.

Rats were shocked in a context on two occasions and then tested for fear reactions as indexed by freezing. Rats spent the interval between conditioning trials and between conditioning and test in their home cages. A short interval between context-conditioning trials or between trials involving a discrete conditioned stimulus (CS) produced better learning than longer intervals. A short retention interval between conditioning and test produced better performance than longer intervals. The effects of the intertrial interval on learning are the opposite of those reported previously and are opposite to those predicted by contemporary learning theories. The effects of the training to test interval on performance are predicted by Wagner's sometimes opponent process (SOP) theory (Wagner, 1981). (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)     

Predator odor as an unconditioned fear stimulus in rats: Elicitation of freezing by trimethylthiazoline, a component of fox feces.

Four experiments tested whether an odor from a rat predator can unconditionally elicit a fear response in rats. In a large chamber, rats displayed fear-related behaviors to trimethylthiazoline (TMT, a volatile compound isolated from fox feces), including avoidance and immobility, while showing less exploratory behavior. In a smaller chamber, TMT induced a species-typical fear response, freezing, whereas other odors did not. In addition, TMT systematically elicited more freezing as the amount of TMT increased. Moreover, there was no within-sessions or between-sessions habituation of freezing to TMT, nor did TMT promote contextual conditioning. The results indicate that the predator odor, TMT, can induce a fear-related behavioral response in rats that is controllable and quantifiable, suggesting that TMT-induced freezing may be a useful paradigm for a neurobehavioral system analysis of ecologically relevant, unconditioned fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: Context discrimination and the effects of retention interval.

Context discrimination and time course studies of contextual fear conditioning revealed strain differences between C57BL/6J (B6) and DBA/2J (D2) mice. Both strains discriminated contexts, but D2 mice exhibited less freezing in a shock-paired context. The strains did not differ immediately, or at 2 and 3 hr after contextual fear conditioning training. D2 mice showed less freezing at 15 min, 30 min, and 24 hr after training. B6 mice exhibited exaggerated generalized freezing and poor discrimination between the context and altered context 7-30 days after training. The acoustic startle response in B6 mice was also enhanced at 14 days after training. D2 mice did not show this pattern of generalized freezing. B6, but not D2, mice retained contextual memories for at least 60 days. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of contextual fear conditioning in rats: Implications for consolidation, infantile amnesia, and hippocampal system function.

Presents developmental evidence that contextual fear conditioning is supported by a short-term memory system that supports conditioning immediately after a shock and by a long-term memory system that supports contextual conditioning 24 hrs after training. This is based on the finding that after 1 conditioning trial, rats 18–32 days old show the same amount of conditioned freezing when tested immediately after conditioning but 18-day-old rats show much less conditioned freezing than the older rats when the retention interval is 24 hrs. The data also suggest that the long-term memory representation of context that mediates conditioned fear is not available until several hours after the conditioning trial. Implications of these findings for memory consolidation processes, infantile amnesia, and hippocampal formation development are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An immediate-shock freezing deficit with discrete cues: A possible role for unconditioned stimulus processing mechanisms.

Five experiments with C57BL/6 mice (Mus musculus) investigated whether failures in shock processing might contribute to deficits in freezing that occur after an animal receives a shock immediately on exposure to a conditioning context. Experiment 1 found that more contextual freezing resulted from delayed shocks than from immediate shocks across 4 shock intensities. Experiment 2 extended the immediate-shock freezing deficit to discrete stimuli. Experiment 3 found that preexposure to the to-be-conditioned cue did not facilitate immediate cued conditioning. Experiment 4 found that context preexposure enhanced context-evoked fear after an immediate shock. Experiment 5 found that context preexposure also enhanced immediate cued conditioning. These findings are problematic for current theories of the immediate-shock freezing deficit that focus exclusively on processing of the conditioned stimulus, and they suggest that failures in shock processing may contribute to the deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential impairment of auditory and contextual fear conditioning by protein synthesis inhibition in C57BL/6N mice.

A 1-trial fear conditioning was used to investigate the temporal development of fear responses expressed as increase of freezing or heart rate and its impairment by the protein synthesis inhibitor cycloheximide (CHX) in male C57BL/6N mice. Heart rate was measured with an implanted transmitter. In the memory tests, mice were exposed to tone and context provided either as foreground or background stimulus during training. The fear responses developed differently from 0 to 24 hr after training under these 3 conditions. A single pretraining CHX injection impaired both memory forms, whereas a single posttraining CHX injection impaired tone- but not context-dependent memory, with the context provided as background stimulus. It was concluded that consolidation of tone-, foreground context-, and background context-dependent fear conditioning may be mediated by partly different neuronal or partly different biochemical pathways, or both. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repeated restraint stress facilitates fear conditioning independently of causing hippocampal CA3 dendritic atrophy.

This study investigated whether 21 days of restraint stress (6 hr/day) and the subsequent hippocampal dendritic atrophy would affect fear conditioning, a memory task with hippocampal-dependent and hippocampal-independent components. Restraint-stressed rats were injected daily (21 days) with tianeptine (10 mg/kg; to prevent hippocampal atrophy) or vehicle then tested on fear conditioning (Days 23-25, with 2 tone-shock pairings) and open field (Day 25). Restraint stress enhanced freezing to context (hippocampal-dependent behavior) and tone (hippocampal-independent) and decreased open-field exploration, irrespective of whether tianeptine was given. Results confirmed that stress produced CA3 dendritic atrophy and tianeptine prevented it. Moreover, CA3 dendritic atrophy was not permanent but reversed to control levels by 10 days after the cessation of restraint stress. These data argue that different neural substrates underlie spatial recognition memory and fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)