Posttraining handling facilitates memory for auditory-cue fear conditioning in rats

A large number of studies have indicated that stress exposure or the administration of stress hormones and other neuroactive drugs immediately after a learning experience modulates the consolidation of long-term memory. However, there has been little investigation into how arousal induced by handling of the animals in order to administer these drugs affects memory. Therefore, the present study examined whether the posttraining injection or handling procedure per se affects memory of auditory-cue classical fear conditioning. Male Sprague-Dawley rats, which had been pre-handled on three days for 1 min each prior to conditioning, received three pairings of a single-frequency auditory stimulus and footshock, followed immediately by either a subcutaneous injection of a vehicle solution or brief handling without injection. A control group was placed back into their home cages without receiving any posttraining treatment. Retention was tested 24 h later in a novel chamber and suppression of ongoing motor behavior during a 10-s presentation of the auditory-cue served as the measure of conditioned fear. Animals that received posttraining injection or handling did not differ from each other but showed significantly less stimulus-induced movement compared to the non-handled control group. These findings thus indicate that the posttraining injection or handling procedure is sufficiently arousing or stressful to facilitate memory consolidation of auditory-cue classical fear conditioning.     

Effects of social defeat on acute cardiovascular response in salt-sensitive and salt-resistant rats

We studied the effects of social stress (SS) and a high salt diet on systolic blood pressure (SBP) and heart rate (HR): S/JR male rats (which exhibit marked elevations in SBP when placed on a high sodium diet) and R/JR male rats (which are resistant to the BP-elevating effects of a high sodium diet) were maintained on a low sodium diet (0.3% NaCl) or placed on a high sodium diet (8% NaCl). Within each dietary condition independent groups were either exposed to SS, by placement in the cage of a trained fighter male (Long-Evans breed) for 25 min, or exposed to no stress. The dietary regimen was imposed for 10 days with stress exposures on Days 1, 2, 3, 5, 7, and 9, with SBP and HR measured indirectly by tail plethysmography 3 min following exposure to SS. SS produced an acute decrease in SBP (20-30 mm Hg) in S/JR rats on the second and subsequent exposures, but did not affect HR. SS did not affect SBP of R/JR rats, but did produce a significant elevation of HR. Maintenance on the high sodium diet increased SBP in S/JR, but not R/JR, rats when it was measured on the eighth (no stress) day, but SS obscured the effects of diet on SBP on days when rats were stressed. Following exposure to attacks, defeated SS rats displayed an upright submissive posture relatively late during the first stress exposure when no change in SBP was observed after SS in S/JRs, but displayed the submissive posture immediately and with long duration on the second and subsequent exposures when a marked decrement in SBP was seen.     

Intra-medial prefrontal administration of SCH-23390 attenuates ERK phosphorylation and long-term memory for trace fear conditioning in rats

The prefrontal cortex is known to be involved in the acquisition of trace conditioning, a higher-cognitive form of Pavlovian conditioning in which a conditioned stimulus and an unconditioned stimulus are separated by a time gap. We have recently reported that medial prefrontal (mPFC) extracellular-signal regulated kinase (Erk) phosphorylation is involved in the long-term memory storage of trace fear conditioning. Because of the important role dopamine D1 receptors play in prefrontal function, such as working memory, and due to evidence that dopamine D1 receptor activity can modulate plasticity, we investigated their role in prefrontal Erk phosphorylation following trace fear conditioning. We found that inhibition of dopamine D1 receptors through intra-mPFC infusion of SCH-23390 (1 microg/0.5 microL) 15 min prior to trace fear conditioning resulted in a decrease in training-related Erk phosphorylation. Additionally, pre-training intra-mPFC infusion of SCH-23390 also resulted in the impairment of long-term retention of CS-US association. These findings implicate mPFC dopamine D1 receptor activity in the storage of long-term memory for higher-cognitive associative tasks.     

Pharmacological dissociation of trace and long-delay fear conditioning in young rats

In most studies comparing trace and delay conditioning, CS duration is kept constant across training conditions but the interstimulus interval (ISI), the time from CS onset to US onset, is confounded. In the infrequently used long-delay condition, however, ISI is kept constant across the trace and delay conditions but CS duration varies. A recent study reported that trace and long-delay fear conditioning have the same developmental trajectory, with both emerging later in development than standard-delay conditioning (). Past studies have shown that trace conditioning is mediated by the cholinergic system; given the parallel developmental emergence of trace and long-delay conditioning, the present study examined whether the cholinergic system also mediates long-delay conditioning. Two experiments, both involving Sprague-Dawley-derived rats and using freezing as a measure of learned fear, showed that the cholinergic system is critically involved in trace conditioning but is not involved in long-delay conditioning. Specifically, pre-training injections of the muscarinic receptor antagonist scopolamine impaired acquisition of a CS-US association in 32-day-old rats trained with a trace procedure but had no effect on rats this age trained with a long-delay procedure (Experiment 1). Similarly, pre-training injections of physostigmine, a cholinesterase inhibitor, enhanced acquisition of trace conditioning in 25-day-old rats but had no effect on long-delay conditioning in rats this age (Experiment 2). Taken together, the results indicate that despite the similarities between trace and long-delay conditioning in terms of developmental emergence and level of conditioned responding, they are mediated by different physiological systems.     

Enduring deficits in contextual and auditory fear conditioning after adolescent, not adult, social instability stress in male rats

Adolescence is a time of developmental changes and reorganization in the brain and stress systems, thus, adolescents may be more vulnerable than adults to the effects of chronic mild stressors. Most studies, however, have not directly compared stress experienced in adolescence to the same stress experience in adulthood. In the present study, adolescent (n=46) and adult (n=48) male rats underwent 16 days of social instability stress (daily 1h isolation and change of cage partners) or were non-stress controls. Rats were then tested on the strength of acquired contextual and cued fear conditioning, as well as extinction learning, beginning either the day after the stress procedure or 3 weeks later. No difference was found among the groups during the Training Phase of conditioning. Irrespective of the time between the social stress experience and fear conditioning, rats stressed in adolescence had decreased context and cue memory, and cue generalization compared to control rats, as measured by the percentage of time spent freezing in tests. Social instability stress in adulthood had no effect on any measure of fear conditioning. The results support the hypothesis that adolescence is a time of heightened vulnerability to stressors.     

Spared anterograde memory for shock-probe fear conditioning after inactivation of the amygdala

Previous studies have shown that amygdala lesions impair avoidance of an electrified probe. This finding has been interpreted as indicating that amygdala lesions reduce fear. It is unclear, however, whether amygdala-lesioned rats learn that the probe is associated with shock. If the lesions prevent the formation of this association, then pretraining reversible inactivation of the amygdala should impair both acquisition and retention performance. To test this hypothesis, the amygdala was inactivated (tetrodotoxin; TTX; 1 ng/side) before a shock-probe acquisition session, and retention was tested 4 d later. The data indicated that, compared with rats infused with vehicle, rats infused with TTX received more shocks during the acquisition session, but more importantly, were not impaired on the retention test. In Experiment 2, we assessed whether the spared memory on the retention test was caused by overtraining during acquisition. We used the same procedure as in Experiment 1, with the exception that the number of shocks the rats received during the acquisition session was limited to four. Again the data indicated that amygdala inactivation did not impair performance on the retention test. These results indicate that amygdala inactivation does not prevent the formation of an association between the shock and the probe and that shock-probe deficits during acquisition likely reflect the amygdala's involvement in other processes.     

Heart rate reactivity in HAD and LAD rats during Pavlovian fear conditioning

Recently, we reported that High-Alcohol-Drinking (HAD) rats exhibited selective deficits in active avoidance learning under alcohol-naive conditions, and that administration of moderate doses of alcohol (0.5 and 1.0 g/kg) facilitated learning in these rats (Blankenship et al., 2000; Rorick et al., 2003b). We hypothesized that the deficits resulted from excessive fear in the aversive learning context and that the anxiolytic properties of alcohol may have contributed to the improved learning that was observed after alcohol administration. This hypothesis was supported by a recent study in which prolonged freezing in HAD rats was seen after a classical fear conditioning procedure (Rorick et al., 2003a). To provide additional evidence that HAD rats indeed exhibit behaviors consistent with the expression of increased fear in aversive learning contexts, we employed a Pavlovian fear conditioning task to measure heart rate in HAD and Low-Alcohol-Drinking (LAD) rats. In this study, HAD (HAD-1 and HAD-2) and LAD (LAD-1 and LAD-2) rats were assigned to one of three pre-exposure conditions: Context Only, Context/Tone, or Sequential (Context Only followed by Context/Tone) Pre-Exposure. Following pre-exposure, fear conditioning acquisition and extinction procedures were identical for all groups. Results indicated that although no baseline differences were observed between HAD and LAD rats, HAD rats receiving Context-Only pre-exposure exhibited excessive heart rate reactivity to the tone conditional stimulus during fear conditioning acquisition, compared to LAD rats receiving the same pre-exposure conditions. These findings support the hypothesis that HAD rats exhibit behaviors consistent with increased fear in aversive learning contexts, as measured by autonomic conditioning.     

Auditory specific fear conditioning results in increased levels of synaptophysin in the basolateral amygdala

Auditory fear conditioning is one of the most well characterized models used in studies of learning and memory. In order to ensure the animals have been conditioned to fear the auditory stimulus, animals are generally tested for their response to this stimulus in a different context to that used for training. For this reason it is often unclear how much contextual fear conditioning the animals also acquire when they are trained. In this study, we have established a protocol for fear conditioning in mice which is explicit for auditory cues; mice trained using this protocol, show a very low fear response to contextual cues encountered during training. We have undertaken analysis to look for potential brain changes associated with this model by measuring levels of the synaptic vesicle protein, synaptophysin, in the basolateral nuclei of the amygdala following auditory fear conditioning. Our results show levels of synaptophysin were significantly higher in mice which learnt to associate the auditory stimulus with fear, in comparison to all non-learning control animals. These findings support the idea that synaptic plasticity associated with formation of fear conditioning to a single specific conditioned stimulus occurs within the basolateral nuclei of the amygdala. Furthermore, our results demonstrate the usefulness of this model in looking for changes in the brain specific for a defined learning event.     

The mirror effect in recognition memory

The mirror effect in recognition memory refers to the fact that, with several different classes of stimuli, performance on new items from each class mirrors (is correlated with) performance on the corresponding classes of old items. Classes of stimuli that are accurately recognized as old when old are also accurately recognized as new when new; those that are poorly recognized as old when old are also poorly recognized as new when new. The statement above is shown not to be a tautology. A survey demonstrates that the effect holds for several types of variables (ways to classify stimuli)—word frequency, concreteness, meaningfulness, and others. The survey includes a total of 80 findings. The theoretical implications of the effect are considered.     

Dominance status predicts social fear transmission in laboratory rats

Acquiring information about stimuli that predict danger, through either direct experience or inference from a social context, is crucial for individuals’ ability to generate appropriate behaviors in response to threats. Utilizing a modified demonstrator–observer paradigm (fear conditioning by proxy) that allows for free interaction between subjects, we show that social dominance hierarchy, and the interactive social behaviors of caged rats, is predictive of social fear transmission, with subordinate rats displaying increased fear responses after interacting with a fear-conditioned dominant rat during fear retrieval. Fear conditioning by proxy conserves some of the pathways necessary for direct fear learning (e.g., lateral amygdala) but is unique in that it requires regions necessary for emotional regulation (e.g., anterior cingulate cortex), making this paradigm an important tool for evaluating learning and behavior in the laboratory setting.     

Deficits in trace cued fear conditioning in galanin-treated rats and galanin-overexpressing transgenic mice

Galanin inhibits the release of several neurotransmitters and produces performance deficits in a variety of spatial and aversive learning and memory tasks. The experiments in this study investigated the role galanin has in emotional learning and memory using a standard delay cued and contextual fear conditioning task. Rats were administered galanin into the lateral ventricles before training, and scored for freezing behavior in the same context and in a novel context with and without an auditory cue (CS) that had been paired previously with an aversive stimulus (US). Galanin-overexpressing transgenic mice were tested in an identical behavioral protocol. The galanin-administered rats and the transgenic mice were not significantly different from their respective controls on this task. A more challenging trace cued and contextual fear conditioning procedure was administered to separate groups of galanin-treated rats and galanin-overexpressing transgenic mice. Subjects were trained with the same CS and US, however, a 2.5-sec delay was inserted between CS offset and US onset. Following the trace conditioning, rats administered galanin and mice overexpressing galanin both exhibited significantly less freezing to the CS in the novel context as compared with their control groups. These results indicate that the observed disruption of cued fear conditioning was specific to the more difficult trace conditioning task. These findings are the first demonstration that galanin impairs performance on an emotional memory task and support the hypothesis that galanin-induced deficits are specific to more difficult cognitive tasks.     

Pentylenetetrazole as an unconditioned stimulus for olfactory and contextual fear conditioning in rats

The association of five footshocks with a neutral odor is able to establish an olfactory fear conditioning in rats. The present study sought to investigate whether the systemic administration of pentylenetetrazole (PTZ; 3.75–15 mg/kg) would turn the coffee odor in a conditioned stimulus in the fear conditioning paradigm. The results showed that rats started to display risk assessment and avoidance after PTZ (15 mg/kg)–coffee odor pairing. When three mild footshocks (0.4 mA for 2 s) were delivered during this pairing, the conditioned response exhibited was greater than before. In both cases, however, pretreatment with the benzodiazepine midazolam (MDZ. 0.5 mg/kg i.p.) fully counteracted the expression of these defensive behaviors. Moreover, after being paired with 15 mg/kg of PTZ alone or combined with footshocks, the coffee odor was able to promote a new fear conditioning related to the context where it was re-exposed. The present findings point out the usefulness of PTZ as an unconditioned stimulus to promote fear conditioning to olfactory and contextual cues in rats.     

Theoretical mechanisms underlying the trial-spacing effect in Pavlovian fear conditioning.

Contemporary explanations of the trial-spacing effect (TSE) were evaluated. Experiment 1 revealed, in rats given tone-footshock trials with 15-, 60-, or 900-s intertrial intervals (ITIs), a direct relationship between freezing to the tone and ITI (the TSE) but an inverted U-shaped relationship between freezing to the training context and ITI. In Experiment 2, footshock preexposure eliminated the TSE that otherwise occurs across 15- to 60-s ITIs but had no effect on the TSE that occurs across 60- to 900-s ITIs. In Experiments 3 and 4, neither (a) increasing posttraining exposure to the training context in rats trained with 60-s ITIs nor (b) reducing between-trial exposure to this context in rats trained with 900-s ITIs influenced freezing to the tone. These findings suggest that the TSE obtained in this research is due to more than 1 mechanism: 1 responsible for the TSE that occurs with ITIs less than approximately 60 s and another responsible for the TSE that occurs with ITIs greater than this. Although the perceptual-defensive-recuperative model may correctly describe the former mechanism, none of the theories tested seems to correctly describe the latter.     

The effect of orienting tasks on recognition memory

The effect of orienting tasks on recognition memory for words and faces was investigated. It was found that relevant orienting tasks improved recognition memory for both classes of stimuli compared with a nonrelevant orienting task and the control condition of testing recognition memory without an orienting task. Attention is drawn to the possibility of qualitative differences between recall and recognition for the effect of orienting tasks. The findings are related to recognition theories. It is suggested that the findings lend support to those theories which hold that retrieval processes play a major role in recognition memory.     

Memory enhancement of classical fear conditioning by post-training injections of corticosterone in rats

There is extensive evidence that post-training administration of the adrenocortical hormone corticosterone facilitates memory consolidation processes in a variety of contextual and spatial-dependent learning situations. The present experiments examine whether corticosterone can modulate memory of auditory-cue classical fear conditioning, a learning task that is not contingent on contextual or spatial representations. Male Sprague-Dawley rats received three pairings of a single-frequency auditory stimulus and footshock, followed immediately by a post-training subcutaneous injection of either corticosterone (1.0 or 3.0mg/kg) or vehicle. Retention was tested 24h later in a novel test chamber and suppression of ongoing motor behavior served as the measure of conditioned fear. Corticosterone dose-dependently facilitated suppression of motor activity during the 10-s presentation of the auditory cue. As corticosterone administration did not alter responding after unpaired presentations of tone and shock, tone alone, shock alone or absence of tone/shock, the findings indicated that corticosterone selectively facilitated memory of the tone-shock association. Furthermore, injections of corticosterone given 3h after training did not alter motor activity during retention testing, demonstrating that corticosterone enhanced time-dependent memory consolidation processes. These findings provide evidence that corticosterone modulates the consolidation of memory for auditory-cue classical fear conditioning and are consistent with a wealth of data indicating that glucocorticoids can modulate a wide variety of emotionally influenced memories.     

Effects of agreement and disagreement in groups on recognition memory performance and confidence

Three dependent variables, derived from an extended Signal-Detection paradigma, were used in each of 3 experiments: memory performance, confidence-level, and response-bias. Each memory item was first judged by S and then fictitiously by 2 confederates providing different degrees of agreement and disagreement. As compared to agreement moderate disagreement yielded both better recognition performance and, if S's judgements were false, less confidence. Strong disagreement failed to repeat these findings. Balanced agreement/disagreement raised the level of both performance and confidence relative to a situation without information from the group. In all the experiments correct decisions yielded higher confidence than errors. Festinger's theory of social comparison processes accounts for all results in performance, but for explaining the confidence shifts assumptions on ‘internal cues’ should also be incorporated. The response-bias was not affected by social treatment differences, thus supporting the view of some Signal-Detection theorists. Proposals towards a general theory of stimulus processing in social context are outlined and some of its consequences are discussed by taking as examples some conformity experiments.     

The mere exposure effect and recognition memory

This investigation explores the relationship between liking ratings and recognition performance for obscure classical and Russian music melodies. Past studies have explored if awareness of stimulus presentation affects the mere exposure effect (MEE) (Bornstein, 1989; Bornstein & D'Agostino, 1992). We investigate if the type of awareness (i.e., "remembering" an actual occurrence of hearing the melody vs. "knowing" that one is familiar with the melody in a more general, less contextualised sense; Tulving, 1985) affects the MEE. In Experiment 1, we administered the liking test and the recognition test within the same test block and found that liking ratings for "remembered" melodies were on average higher than those for melodies that were merely "known". Although the recognition data replicate the findings of Gardiner, Kaminska, Dixon, and Java (1996) whereby remember and know responses to a given stimulus react differently to repetition from one to three trials, liking data did not vary with the degree of exposure. In addition, our adoption of the recognition category "guess" resulted in a pattern of results that is not only different from previous studies but illustrates the importance of judged, instead of true, old/new status in determining liking. The basic findings of Experiment 1 were replicated in Experiment 2 in which the liking test was conducted prior to the recognition test. Implications of these findings for theories of MEE are discussed.