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There is now ample evidence that the strength and underlying mechanisms of memory formation can be drastically altered by prior experience. However, the prior work using rodent models on this topic has used only males as subjects, and as a result, we do know whether or not the effects of prior experience on subsequent learning are similar in both sexes. As a first step towards addressing this shortcoming, rats of both sexes were given auditory fear conditioning, or fear conditioning with unsignaled shocks, followed an hour or a day later by a single pairing of light and shock. Fear memory for each experience was assessed by measuring freezing behavior to the auditory cue and fear-potentiated startle to the light. Results showed that males trained with auditory fear conditioning showed facilitated learning to the subsequent visual fear conditioning session when the two training sessions were separated by one hour or one day. Females showed evidence of facilitation in rats given auditory conditioning when they were spaced by an hour but not when they were spaced by one day. Contextual fear conditioning did not support the facilitation of subsequent learning under any conditions. These results indicate that the mechanism by which prior fear conditioning facilitates subsequent learning differs between sexes, and they set the stage for mechanistic studies to understand the neurobiological basis of this sex difference. [ABSTRACT FROM AUTHOR]

The degree of generalization from a fearful context to other contexts is determined by precision of the original fear memory. Experiences before and after fear learning affect memory precision. Pre-exposure to a similar context before context conditioning results in increased generalization to the similar context. In contrast, exposure to the conditioning context after fear learning reduces fear generalization. In the current study we aimed to investigate whether the events before and after fear learning interact. We hypothesized that pre-exposure-induced enhanced generalization could be reduced by a return to the conditioning context. We found that, in contrast to previous findings, pre-exposure did not affect generalization. However, a reminder of the conditioning context reduced generalization to both a similar and a different context. The results stress the dynamic nature of emotional memory. [ABSTRACT FROM AUTHOR]

Earlier studies have shown that a latent inhibitor is poor at competing for learning with another conditioned stimulus on a compound conditioning trial. Previous research also has shown that the poor conditioned response produced to a latent inhibitor can be reversed by a retention interval placed after conditioning and prior to testing the conditioned response. In the present conditioned taste aversion experiments, a CS flavor (“A”) was given CS-alone preexposures prior to a pairing of the CS with the US. A serial compound conditioning phase then occurred in which this CS was able to compete with an added novel CS (“B”) when the two CSs were paired with the US. However, prior to the compound conditioning phase, a retention interval occurred lasting either one day or many days (15 days in one experiment and 21 days in another experiment). It was found that the lengthy retention interval enhanced the competitive potential of the pretrained CS. These results show that treatments that enhance the expression of a CS-US association can also enhance the competitive ability of the CS. [ABSTRACT FROM AUTHOR]

Time plays an important role in conditioning, it is not only possible to associate stimuli with events that overlap, as in delay fear conditioning, but it is also possible to associate stimuli that are discontinuous in time, as shown in trace conditioning for a discrete stimuli. The environment itself can be a powerful conditioned stimulus (CS) and be associated to unconditioned stimulus (US). Thus, the aim of the present study was to determine the parameters in which contextual fear conditioning occurs by the maintenance of a contextual representation over short and long time intervals. The results showed that a contextual representation can be maintained and associated after 5 s, even in the absence of a 15 s re-exposure to the training context before US delivery. The same effect was not observed with a 24 h interval of discontinuity. Furthermore, optimal conditioned response with a 5 s interval is produced only when the contexts (of pre-exposure and shock) match. As the pre-limbic cortex (PL) is necessary for the maintenance of a continuous representation of a stimulus, the involvement of the PL in this temporal and contextual processing was investigated. The reversible inactivation of the PL by muscimol infusion impaired the acquisition of contextual fear conditioning with a 5 s interval, but not with a 24 h interval, and did not impair delay fear conditioning. The data provided evidence that short and long intervals of discontinuity have different mechanisms, thus contributing to a better understanding of PL involvement in contextual fear conditioning and providing a model that considers both temporal and contextual factors in fear conditioning. [ABSTRACT FROM AUTHOR]

Many studies suggest that fear conditioning influences sleep. It is, however, not known if the changes in sleep architecture after fear conditioning are essentially associated with the consolidation of fearful memory or with fear itself. Here, we have observed that within sleep, NREM sleep consistently remained augmented after the consolidation of cued fear-conditioned memory. But a similar change did not occur after impairing memory consolidation by blocking new protein synthesis and glutamate transmission between glial-neuronal loop in the lateral amygdala (LA). Anisomycin (a protein synthesis inhibitor) and DL-α–amino-adipic acid (DL- α -AA) (a glial glutamine synthetase enzyme inhibitor) were microinjected into the LA soon after cued fear-conditioning to induce memory impairment. On the post-conditioning day, animals in both the groups exhibited significantly less freezing. In memory-consolidated groups (vehicle groups), NREM sleep significantly increased during 2nd to 5th hours after training compared to their baseline days. However, in memory impaired groups (anisomycin and DL- α -AA microinjected groups), similar changes were not observed. Our results thus suggest that changes in sleep architecture after cued fear-conditioning are indeed a consolidation dependent event. [ABSTRACT FROM AUTHOR]

A key barrier to changing unhealthy eating habits is the current food-rich environment. Today, there are many palatable food cues that trigger unhealthy eating habits, and once a habit is strongly engrained, it becomes very difficult to change. This research examined the effects of diet priming that is a type of cueing intervention that activates a dieting goal in a tempting situation and thus reduces unhealthy eating behavior in line with the dieting goal. This research was conducted both in a laboratory and in two field experiments. In the three experiments, participants were randomly assigned to conditions where they were either primed by an image of a slim model associated with dieting (priming condition) or were presented with an image of an animal unrelated to dieting (control condition). The dependent variable was the number of snacks that participants took in the laboratory in Study 1 and the number of snacks consumed within the next two weeks in a daily setting in Study 2 and 3. The three studies showed that unhealthy eating habits strongly affect general eating behavior. However, in this research, diet priming changed the influence of unhealthy eating habits and resulted in the decrease of unhealthy eating. Exposure to diet priming cues moderated the influence of unhealthy eating habits triggered by palatable food cues in today's food-rich environment. These findings suggest that diet priming can change habitual reactions to temptations associated with unhealthy eating. Implications for diet priming as an intervention for unhealthy eating habits are discussed herein. [ABSTRACT FROM AUTHOR]

We previously showed that a single weak fear conditioning trial, that does not produce a long-term fear memory (LTM), appeared to prime memory formation such that when a second trial followed within a circumscribed time window a robust and long-lasting fear memory was formed. We also showed that this priming effect could be blocked if we interfered with protein kinase A (PKA) signaling in the amygdala during the first conditioning trial. The goals of the current study were to determine if LTM formation after the second trial depends on PKA signaling in the amygdala and to characterize the underlying memory processes engaged during the second trial that allows for LTM formation. Our interpretation of the original findings is that the second conditioning trial triggers LTM from a metaplastic state that is engaged by the first conditioning trial. However, it is also possible that the second conditioning trial acts as a reminder of the first and engages a reconsolidation-like process. Several experiments were conducted to distinguish between these two possibilities. We show that interfering with PKA signaling during the second conditioning trial disrupts memory formation. However, if a third trial follows the second or if the second trial was presented without shock, the PKA inhibitor was no longer effective. Our findings demonstrate that the induction of fear memory from a metaplastic state involves new learning that is distinct from retrieval-dependent updating of memories. [ABSTRACT FROM AUTHOR]

Abstract: Disruption of the reconsolidation of conditioned fear memories has been suggested as a non-pharmacological means of preventing the return of learned fear in human populations. A reconsolidation update paradigm was developed in which a reconsolidation window is opened by a single isolated retrieval trial of a previously reinforced CS+ which is then followed by Extinction Training within that window. However, follow-up studies in humans using multi-methods fear conditioning indices (e.g., fear-potentiated startle, skin conductance, US-expectancy) have failed to replicate the retrieval+extinction effects. In the present study, we further investigated the retrieval+extinction reconsolidation update paradigm by directly comparing the acquisition, extinction, and return of fear-potentiated startle in the absence or presence of US-expectancy measures (using a trial-by-trial response keypad) with and without retrieval of a previously acquired CS-US association. Participants were fear conditioned to two visual cue CS+’s, one of which was presented as a single, isolated retrieval trial before Extinction Training and one that was extinguished as usual. The results show that the inclusion of US-expectancy measures strengthens the CS–US association to provide enhanced fear conditioning and maintenance of fear memories over the experimental sessions. In addition, in the groups that used on-line US-expectancy measures, the retrieval+extinction procedure reduced reinstatement of fear-potentiated startle to both previously reinforced CS+’s, as compared to the extinction as usual group. [Copyright &y& Elsevier]

Highlights: [•] A novel associative learning phenotype of forebrain neuronal GlyT1 is demonstrated. [•] The sensitivity to the CS–US contiguity in Pavlovian learning is enhanced. [•] This complements the previous report of increased sensitivity to CS pre-exposure. [•] Neuronal GlyT1 may weaken as well as strengthen the conditioned response. [•] The temporal expression of the conditioned response may also be modified. [ABSTRACT FROM AUTHOR]

Abstract: Responding to bivalent stimuli (i.e., stimuli with features relevant for different tasks) slows subsequent performance. In prospective memory research, prospective memory targets can be considered as bivalent stimuli because they typically involve features relevant for both the prospective memory task and the ongoing task. The purpose of this study was to investigate how responding to a prospective memory target slows subsequent performance. In two experiments, we embedded the prospective memory task in a task-switching paradigm and we manipulated the degree of task-set overlap between the prospective memory task and the ongoing task. The results showed consistent after-effects of responding to prospective memory targets. The specific trajectory of the slowing depended on the amount of task-set overlap. These results demonstrate that responding to prospective memory targets results in after-effects, a so far neglected cost on ongoing task performance. [Copyright &y& Elsevier]

Abstract: Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatal function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long–Evans rats were ovariectomized, treated with 17β-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for 2days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5μg/kg) but not high dose (45μg/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4mg of genistein over 2days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling through estrogen receptor β and membrane-associated estrogen receptors in learning enhancements and impairments given the preferential binding of genistein to the ERβ subtype and affinity for GPER. [Copyright &y& Elsevier]

Abstract: The learning of new information and recall of that information presumably involves modification of and access to shared circuitry in the brain. However, learning and recall may involve the activation of distinct parts of that circuitry, according to the quite distinct functional differences between these two processes. Previously we examined neuronal activation following learning of context fear conditioning. Using the Fos-Tau-LacZ (FTL) transgenic mouse to label activated neurons, we identified a number of distinct populations of neurons in amygdala and hypothalamus which showed learning specific activation. These populations of neurons showed much less activation following recall. Here we ask what populations of neurons might be specifically activated following recall. We trained mice in context fear conditioning, and then looked at FTL activation following recall of context fear. We identified a number of populations of neurons which showed recall specific activation in nucleus accumbens shell, the anterio-medial bed nucleus of stria terminalis, the anterior commissural nucleus and the periventricular hypothalamic nucleus. These were all different populations of neurons compared with those activated following context fear learning. These different functional activation patterns occurring between learning and recall may reflect the different brain functions occurring between these two memory related processes. [Copyright &y& Elsevier]

Abstract: Evaluative conditioning (EC) refers to the effect that pairings of a conditioned stimulus (CS) with a valenced unconditioned stimulus (US) lead to changes in the evaluation of the CS. There have been recurring debates about whether EC requires awareness of the contingency between CSs and USs during learning. We argue that the memory performance data obtained in the standard paradigm remain ambiguous about the role of contingency awareness during the encoding of CS–US pairings. First, memory performance data are unable to distinguish between encoding-related versus retrieval-related effects. Second, the relation between memory performance and evaluation is correlational, which limits conclusions about causal relations between memory performance and EC effects. These ambiguities imply that any possible data pattern can be interpreted in at least two different ways. It is concluded that a resolution of the current debate requires alternative approaches in which contingency awareness is experimentally manipulated during the encoding of CS–US pairings. [Copyright &y& Elsevier]

Abstract: Specific neuronal subpopulations within specific brain areas are responsible for learning and memory. A fear memory engages a subset of lateral amygdala neurons, but whether multiple contextual fear memories engage the same or different subsets of lateral amygdala neurons remains unclear. Here, we demonstrate the representation of multiple contextual fear memories in the amygdala with cellular and temporal resolution using a large-scale imaging method. Mice were conditioned with a footshock in 2 separate chambers. They were then re-exposed to either the same conditioning chamber twice or 2 different conditioning chambers. The activities of individual neurons related to the re-exposures were determined by the subcellular distribution of Arc/Arg3.1 RNA. Reactivation of different memories activated partially (about 50%) overlapping neurons, whereas reactivation of the same memory activated more overlapping (about 65%) neurons. These findings indicate that lateral amygdala neurons related to different fear memories are partly common, and that a small but significant neuronal population (2.7% of total lateral amygdala neurons) encodes differences in individual fear memories. Moreover, memory retrieval increased the size of the neuronal subpopulation activated during subsequent retrieval. Taken together, our findings indicate that small plastic subsets of neurons encode fear memories from individual contexts. [Copyright &y& Elsevier]

Abstract: Emotional influences on memory for events have long been documented yet surprisingly little is known about how emotional signals conveyed by contextual cues influence memory for face identity. This study investigated how positively and negatively valenced contextual emotion cues conveyed by body expressions or background scenes influence face memory. The results provide evidence of emotional context influence on face recognition memory and show that faces encoded in emotional (either fearful or happy) contexts (either the body or background scene) are less well recognized than faces encoded in neutral contexts and this effect is larger for body context than for scene context. The findings are compatible with the hypothesis that emotional signals in visual scenes trigger orienting responses which may lead to a less elaborate processing of featural details like the identity of a face, in turn resulting in a decreased facial recognition memory. [Copyright &y& Elsevier]

Abstract: Rats were able to search multiple food cups in a foraging task and successfully return to a fixed, but not a variable, start location. Reducing the number of food cups to be searched resulted in an improvement in performance in the variable start condition. Performance was better when only one or two food cups had to be visited but was still impaired if the food was not found in the first cup searched. Variable start locations impaired performance when only one food cup had to be searched, if that cup was moved over the table. These findings suggest that there is an interaction between memory processes and the navigational processes that allows an animal to return to its start location after a foraging trip. It appears that a fixed location for the food or the start point of a foraging trip is a necessary precondition for accurate performance. [Copyright &y& Elsevier]

Abstract: Experiments 1 and 2 involved independent groups that received primary reinforcement after a correct match with a probability of 1.0, .50 or .25. Correct matches that did not produce primary reinforcement produced a conditioned reinforcer. Both experiments revealed little evidence that acquisition or retention was adversely affected by use of intermittent reinforcement. Experiment 3 involved a group that received 100% reinforcement and two others that received 25% reinforcement, one of which received conditioned reinforcement and the other did not. Following acquisition and retention testing, birds in group 100% and group 25% with conditioned reinforcement were exposed to 25% reinforcement and no conditioned reinforcement. Results revealed that conditioned reinforcement was important in promoting acquisition but was irrelevant in maintaining performance. It was concluded that intermittent reinforcement, especially when combined with conditioned reinforcement during acquisition, supports levels of acquisition and retention comparable to that of continuous reinforcement. Theoretically, the findings are consistent with an extension of Blough''s instance-based theory of discrimination performance and, practically, they suggest that use of intermittent reinforcement could result in increased efficiency and economy in labs using delayed matching. [Copyright &y& Elsevier]

Abstract: Contextual fear conditioning emerges around post-natal day (PD) 23 in the rat. This is thought to reflect hippocampus-dependent conjunctive learning, which binds the individual features of the context into a unified representation (). However, context conditioning can also be supported by hippocampus-independent, feature-based simple associations () and these may operate at PD 23–24 (). To address this issue, we studied the ontogeny of a variant of contextual fear conditioning, termed the context-preexposure-facilitation-effect (CPFE), in which exposure to context and (immediate) foot shock occur on successive occasions. This variant requires conjunctive as opposed to feature-based simple associations (). We tested PD 17, 24, and 31 rats on the CPFE vs. conventional context conditioning (Exp. 1) and on the CPFE with stronger reinforcement (Exp. 2). The CPFE emerged on PD 24 regardless of reinforcer strength and in parallel with context conditioning. Infusions of the NMDA-receptor antagonist, MK-801, into the dorsal hippocampus just before pre-exposure on PD 24 eliminated the CPFE, whereas infusions occurring after pre-exposure had no effect (Exp. 3). These findings demonstrate a role of hippocampal NMDA receptors in the CPFE as early as PD 24 and implicate conjunctive learning mechanisms in the ontogeny of contextual fear conditioning. [Copyright &y& Elsevier]

Abstract: 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 16days 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 3weeks 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. [ABSTRACT FROM AUTHOR]

Abstract: Just as fear can be learned, it can also be inhibited. The most common way of reducing learned fear is through extinction, where the conditioned stimulus (CS) previously paired with an aversive unconditioned stimulus (US) is repeatedly presented on its own. Another, much less commonly studied, way to inhibit learned fear is by habituating, or devaluing, the US. In this procedure, fear responding to a CS is reduced by repeatedly presenting the US in the absence of the CS following the conditioning phase. The purpose of the present study was to directly compare the effects of US habituation and CS extinction on a learned fear response (freezing). Experiment 1 demonstrated that US habituation given either after (Experiment 1A) or before (Experiment 1B) fear conditioning reduced freezing to the CS at test. We then showed that the reduction in freezing resulting from either US habituation or CS extinction was context-specific (i.e., a change in context led to a renewal of the learned fear response; Experiment 2) and, furthermore, was attenuated when a pre-test shock was given (i.e., reinstatement of fear was observed in both cases; Experiment 3). Finally, Experiment 4 demonstrated that an injection of the NMDA antagonist MK-801 prior to US habituation impaired long-term retention of the learning that takes place during this procedure. Together, these results suggest that the decrement in conditioned fear responses produced by US habituation and CS extinction could rely on overlapping processes. [Copyright &y& Elsevier]

Abstract: Animals develop robust learning and long lasting taste aversion memory once they experience a new taste that is followed by visceral discomfort. A large body of literature has supported the hypothesis that basolateral amygdala (BLA) plays a critical role in the acquisition and extinction of such conditioned taste aversions (CTA). Despite the evidence that BLA is crucially engaged during CTA training, it is unclear how BLA neural activity represents the conditioned tastes. Here, we incorporated a modified behavioral paradigm suitable for single unit study, one which utilizes a sequence of pulsed saccharin and water infusion via intraoral cannulae. After conditioning, we investigated BLA unit activity while animals experience the conditioned taste (saccharin). Behavioral tests of taste reactivity confirmed that the utilized training procedure produced reliable acquisition and expression of the aversion throughout test sessions. When neural activity was compared between saccharin and water trials, half of the recorded BLA units (77/149) showed differential activity according to the types of solution. 76% of those cells (29/38) in the conditioned group showed suppressed activity, while only 44% of taste reactive cells (17/39) in controls showed suppressed activity during saccharin trials (relative to water trials). In addition, the overall excitability of BLA units was increased as shown by altered characteristics of burst activity after conditioning. The changes in BLA activity as a consequence of CTA were maintained throughout test sessions, consistent with the behavioral study. The current study suggests that the neuronal activity evoked by a sweet taste is altered as a consequence of CTA learning, and that the overall change might be related to the learning induced negative affect. [Copyright &y& Elsevier]

Abstract: Recent research, using several experimental models, demonstrated that the histaminergic system is clearly involved in memory formation. This evidence suggested that during different associative learning tasks, histamine receptor subtypes have opposite functions, related to the regulation of cortical cholinergic activity. Given that cortical cholinergic activity and nucleus basalis magnocellularis (NBM) integrity are needed during taste memory formation, the aim of this study was to determine the role of histamine receptors during conditioned taste aversion (CTA). We evaluated the effects of bilateral infusions of 0.5μl of pyrilamine (100mM), an H1 receptor antagonist, into the NBM, or of R-α-methylhistamine (RAMH) (10mM), an H3 receptor agonist, into the insular cortex of male Sprague-Dawley rats 20min before acquisition and/or retrieval of conditioned taste aversion. The results showed that blockade of H1 receptors in NBM or activation of H3 receptors in the insular cortex impairs formation but not retrieval of aversive taste memory. These results demonstrated differential roles for histamine receptors in two important areas for taste memory formation and suggest that these effects could be related with the cortical cholinergic activity modulation during CTA acquisition. [Copyright &y& Elsevier]

Abstract: To investigate the effect of naloxone on a putative memory consolidation process underlying reacquisition of heroin and cocaine conditioned place preference, four studies were conducted in male Sprague–Dawley rats using a common procedure involving: place conditioning (0.3 or 1mg/kg heroin or 20mg/kg cocaine; ×4 sessions), extinction (vehicle×4 sessions), and reconditioning (0 or 1mg/kg heroin or 20mg/kg cocaine; ×1 session). Systemic naloxone injections (0, 1 and 3mg/kg) or bilateral intra-ventral tegmental area (VTA) naloxone methiodide infusions (2nmol in 0.5μl×side) were administered at different times following reconditioning. Post-reconditioning administration of naloxone dose-dependently blocked, attenuated and had no effect on reacquisition of heroin CPP when administered immediately, 1h and 6h after reconditioning, respectively. The highest dose of naloxone also blocked reacquisition of cocaine CPP, and did not produce a conditioned place aversion in heroin-naïve and heroin pre-treated animals. Post-reconditioning infusions in the VTA, but not in adjacent structures, blocked reacquisition of heroin CPP when administered immediately, but not 6h, after reconditioning. These data suggest that reacquisition of drug-cues associations involves a memory consolidation process sensitive to manipulations of the endogenous opioid system, and indicate that opioid receptors in the VTA may be critically involved in the re-emergence of drug seeking behavior. [Copyright &y& Elsevier]

Abstract: The basolateral amygdala complex (BLA) is involved in acquisition of contextual and auditory fear conditioning. However, the BLA is not a single structure but comprises a group of nuclei, including the lateral (LA), basal (BA) and accessory basal (AB) nuclei. While it is consensual that the LA is critical for auditory fear conditioning, there is controversy on the participation of the BA in fear conditioning. Hodological and neurophysiological findings suggest that each of these nuclei processes distinct information in parallel; the BA would deal with polymodal or contextual representations, and the LA would process unimodal or elemental representations. Thus, it seems plausible to hypothesize that the BA is required for contextual, but not auditory, fear conditioning. This hypothesis was evaluated in Wistar rats submitted to multiple-site ibotenate-induced damage restricted to the BA and then exposed to a concurrent contextual and auditory fear conditioning training followed by separated contextual and auditory conditioning testing. Differing from electrolytic lesion and lidocaine inactivation, this surgical approach does not disturb fibers of passage originating in other brain areas, restricting damage to the aimed nucleus. Relative to the sham-operated controls, rats with selective damage to the BA exhibited disruption of performance in the contextual, but not the auditory, component of the task. Thus, while the BA seems required for contextual fear conditioning, it is not critical for both an auditory-US association, nor for the expression of the freezing response. [Copyright &y& Elsevier]

Abstract: Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1–28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cortex (A1) to the frequency of a conditioned stimulus (CS), and the greater the level of CS importance, the larger the area of representational gain [Weinberger, N. M. (2007). Associative representational plasticity in the auditory cortex: A synthesis of two disciplines. Learning & Memory, 14(1–2), 1–16]. The two lines of research suggest that BLA strengthening of memory might be accomplished in part by increasing the representation of an environmental stimulus. The present study investigated whether stimulation of the BLA can affect cortical memory representations. In male Sprague–Dawley rats studied under urethane general anesthesia, frequency receptive fields were obtained from A1 before and up to 75min after the pairing of a tone with BLA stimulation (BLAstm: 100 trials, 400ms, 100Hz, 400μA [±16.54]). Tone started before and continued after BLAstm. Group BLA/1.0 (n =16) had a 1s CS–BLAstm interval while Group BLA/1.6 (n =5) has a 1.6s interval. The BLA/1.0 group did develop specific tuning shifts toward and to the CS, which could change frequency tuning by as much as two octaves. Moreover, its shifts increased over time and were enduring, lasting 75min. However, group BLA/1.6 did not develop tuning shifts, indicating that precise CS–BLAstm timing is important in the anesthetized animal. Further, training in the BLA/1.0 paradigm but stimulating outside of the BLA did not produce tuning shifts. These findings demonstrate that the BLA is capable of exerting highly specific, enduring, learning-related modifications of stimulus representation in the cerebral cortex. These findings suggest that the ability of the BLA to alter specific cortical representations may underlie, at least in part, the modulatory influence of BLA activity on strengthening long-term memory. [Copyright &y& Elsevier]

Abstract: This study extends Duff and Hampson’s [Duff, S., & Hampson, E. (2001). A sex difference on a novel spatial working memory task in humans. Brain and Cognition, 47, 470–493] finding of a sex-related difference in favor of females for an object location memory task. Twenty female and 20 male undergraduate students performed both manual and computer-generated versions of the task using stimuli that varied in degree of verbalizability. A 2×2×3 ANOVA with Sex as a between-subjects factor, and Presentation (manual or computer) and Stimuli (common objects, common shapes, and novel shapes) as within-subjects repeated measures revealed a significant main effect for Sex. Females made fewer errors than males regardless of presentation and across the three levels of verbalizability (i.e., stimulus types); moreover, the effect size was considered “large” [Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Berlin: Springer]. These findings are interpreted within the context of the current literature that demonstrates a female advantage for object location memory (e.g., [Voyer, D., Postma, A., Brake, B., & Imperato-McGinley, J. (2007). Gender differences in object location memory: A meta-analysis. Psychonomic Bulletin and Review, 14, 23–38]). [Copyright &y& Elsevier]

Abstract: It is unclear whether protein phosphatases, which counteract the actions of protein kinases, play a beneficial role in the formation and extinction of previously acquired fear memories. In this study, we investigated the role of the calcium/calmodulin dependent phosphatase 2B, also known as calcineurin (CaN) in the formation of contextual fear memory and extinction of previously acquired contextual fear. We used a temporally regulated transgenic approach, that allowed us to selectively inhibit neuronal CaN activity in the forebrain either during conditioning or only during extinction training leaving the conditioning undisturbed. Reducing CaN activity through the expression of a CaN inhibitor facilitated contextual fear conditioning, while it impaired the extinction of previously formed contextual fear memory. These findings give the first genetic evidence that neuronal CaN plays an opposite role in the formation of contextual fear memories and the extinction of previously formed contextual fear memories. [Copyright &y& Elsevier]

Abstract: In rodents, the expression of a reward-conditioned place preference (CPP) is regulated in a circadian pattern such that the preference is exhibited strongly at the circadian time of prior training but not at other circadian times. Because each animal is trained only at a single circadian phase, the concept of time as a context cue is derived from a rhythmic internal state rather than learned explicitly from the external cues. We now report that the same “time memory” is expressed following context conditioning in the common marmoset (Callithrix jacchus). Animals were trained at a specific time to discriminate between an unpaired context and a context paired with food reward. Marmosets were then tested for preference at circadian times that were either the same or different from the training time. Preference was expressed only when training and testing times matched. The results show that time of day learning can be generalized to this new world primate implying that a similar circadian mechanism might regulate craving for reward in diverse mammals including human beings. [Copyright &y& Elsevier]

Abstract: Repeated spaced training sessions of contingent tactile stimulation to the pneumostome as it opens are required to cause long-term memory (LTM) formation of aerial respiratory behaviour making if difficult to determine exactly when memory forms. We have devised a single-trial aversive operant conditioning training procedure in Lymnaea to be better able to elucidate the causal mechanisms of LTM formation. Observations of baseline breathing behaviour in hypoxia were first made. Twenty-four hours later the snails were trained using the single trial procedure, by placing them in a small Petri dish containing 4ml of 25mM KCl for 30–35s as soon as the first pneumostome opening in hypoxia was attempted. LTM was present if (1) breathing behaviour following training was significantly less than before; and (2) breathing behaviour post-training was significantly less in experimental groups than in yoked control groups. LTM persisted for 24h but not 48h. Yoked controls that received an aversive stimulus not contingent with pneumostome opening had no evidence of memory. Cooling directly after, but not at any other time, blocks LTM formation. LTM formation was also prevented by removal of the cell body of the neuron RPeD1 before training. [Copyright &y& Elsevier]

Abstract: In this study, we analyzed the participation of the entorhinal cortex in extinction of a learned aversive response. Rats with infusion cannulae aimed to the entorhinal cortex were trained in a one-trial step-down inhibitory avoidance task (IA) and submitted to four consecutive daily test sessions without the footshock, a procedure that induced extinction of the conditioned response in control animals. When infused into the entorhinal cortex immediately after the first extinction session at doses able to block consolidation of IA memory, the NMDA receptor antagonist, AP5 (25nmol/side), the inhibitor of protein synthesis anisomycin (300nmol/side) and the inhibitor of CaMKII, KN-93 (10nmol/side), but not the MEK1/2 inhibitor PD-98059 (5nmol/side) hindered extinction of the IA response. The same results were obtained when the interval between the first and second test session was 48 instead of 24h. The data indicate that normal functionality of the NMDA receptors, together with CaMKII activity and protein synthesis are necessary in the entorhinal cortex at the time of the first test session to generate extinction. Our results also suggest that the ERK1/2 pathway does not play a role in this process. [Copyright &y& Elsevier]

Abstract: A time window is a limited period after an event initially occurs in which additional information can be integrated with the memory of that event. It shuts when the memory is forgotten. The time window hypothesis holds that the impact of a manipulation at different points within the time window is nonuniform. In two operant conditioning experiments with 68 3-month-old human infants, we tested the predictive validity of the nonuniformity principle for reinstatement—a partial training trial that forestalls forgetting. After demonstrating that 3-month-olds forget the training task after 5 days (Experiment 1), we presented a reinstatement early (immediately), midway (3 days), or late (5 days) in the time window (Experiment 2). Retention increased exponentially with the reinstatement delay. The surprising magnitude of this result, plus its generality across tasks and species, strongly suggests that the timing of reinstatement differentially affects the outcomes of studies on learning and memory. [Copyright &y& Elsevier]

Abstract: Operant conditioning of aerial respiratory behaviour and its consolidation into long-term memory in Lymnaea has been previously studied in both intact, freely moving snails and in in vitro preparations made from previously trained snails. Here, we show in previously untrained semi-intact in vitro Lymnaea preparations that aerial respiratory behaviour can also be operantly conditioned. Neither yoked control nor ‘run-down’ control procedures in these in vitro preparations result in an alteration of aerial respiratory behaviour. Memory in the operantly trained semi-intact preparations persists for at least 1h after training. Intracellular recordings made from RPeD1, one of the 3-CPG neurons and the neuron that initiates CPG activity; show that there are specific changes in central excitatory input to this neuron concurrent with learning and its consolidation into memory. In addition following the acquisition of learning and its consolidation into memory the ability of RPeD1 and VI/J neurons when depolarized to cause a pneumostome opening is significantly decreased. Thus, previously untrained in vitro semi-intact preparations can be used to study changes in neuronal activity in a neuron known to be both necessary for the behaviour and for memory formation. [Copyright &y& Elsevier]

This paper reviews recent findings about how rats navigate by learning to discriminate among locations. The assumption underlying the experiments and their interpretation is that the information required to do this is learned by three independent, parallel memory systems. One system processes cognitive information (or “knowledge”), a second system processes reinforced stimulus–response associations and a third processes Pavlovian conditioned responses in the form of stimulus–affect associations. The information stored in each system produces behavior that, in some cases, results in a location discrimination. The present experiments focus on three factors that influence what each system learns and whether the resulting memory produces behavior that results in a location discrimination. One factor is whether the locations to be discriminated can be identified by unique, unambiguous stimuli or whether they are ambiguously associated with the same stimuli. The second factor is whether the stimuli are observed passively or whether the rats move among them, voluntarily or involuntarily. The third factor is whether or not the rats perform specific reinforced responses in the presence of the stimuli. Instances of co-operative behavioral outputs from memory systems that facilitate location discriminations and of competitive outputs that impede discriminations are described. [Copyright &y& Elsevier]

Glucocorticoid modulation of emotional memory has repeatedly been shown in aversive learning paradigms, but has received little attention in appetitive tasks. It has also been suggested that it may be selective for contextual cues. In order to investigate if glucocorticoids can modulate memory in discrete-cue conditioning of both appetitive and aversive tasks, two experiments were carried out. Male Lister-Hooded rats received pairings of an auditory cue and either food-reward (experiment 1) or footshock (experiment 2), followed immediately by posttraining injections of the glucocorticoid receptor agonist dexamethasone (0.3, 0.6, and 1.2 mg/kg) or vehicle. Dexamethasone (1.2 mg/kg) led to significantly enhanced learning. These results give support to the notion that glucocorticoids play a role in the modulation of both appetitive and aversive emotional memories and show that their role in learning goes beyond the construction of context representations. The modulation of appetitive and aversive discrete-cue learning may be subserved by a common mechanism. [Copyright &y& Elsevier]

The fimbria-fornix (FF) is the main subcortical input to the hippocampus. It has been shown that FF lesions facilitate performance on a standard-delay two-way active avoidance task (AA2), thought to involve implicit memory. The hippocampal region is required for explicit or relational memory. It has been proposed that the hippocampus and related structures might associate events that are separated in space or time and detect elements shared in common by such discontiguous episodes. Therefore, FF lesions would be expected to impair performance on a trace paradigm, which introduces an interval between the CS (conditioned stimulus) and the US (unconditioned stimulus) and is generally considered a model of explicit memory. We predicted that FF lesions would impair memory in a trace AA2 procedure, while the same lesions would facilitate memory in a standard delay version of the task. To test this hypothesis, two experiments were carried out in 102 male Wistar rats. The first experiment characterized the trace paradigm using this kind of conditioning and demonstrated that control rats were able to acquire and retrieve (24 h and 11 days postacquisition) the association between the CS (tone) and the US (electric foot shock) when a trace interval (5, 10, or 20 s) was interposed between both stimuli. In the second experiment, we investigated the effects of FF electrolytic lesions on the same task using delay and trace (10-s trace interval) paradigms. Surprisingly, FF lesions facilitated the acquisition and the 24-h retention of the AA2 not only on the standart delay paradigm, but also with the trace paradigm. We suggest that facilitative effects could be a result of impairment in contextual learning. [Copyright &y& Elsevier]

Epigenetic modifications allow cells to quickly alter their gene expression and adapt to different stresses. In addition to direct chromatin modifications, prion-like proteins have recently emerged as a system that can sense and adapt the cellular response to stressful conditions. Interestingly, such responses are maintained through prions' self-templating conformations and transmitted to the progeny of the cell that established a prion trait. Alternatively, mnemons are prion-like proteins which conformational switch encodes memories of past events and yet does not propagate to daughter cells. In this review, we explore the biology of the recently described prions found in Saccharomyces cerevisiae including [ ESI + ], [ SMAUG +], [ GAR +], [ MOT3 +], [ MOD +], [ LSB +] as well as the Whi3 mnemon. The reversibility of the phenotypes they encode allows cells to remove traits which are no longer adaptive under stress relief and chaperones play a fundamental role in all steps of prion-like proteins functions. Thus, the interplay between chaperones and prion-like proteins provides a framework to establish responses to challenging environments. [ABSTRACT FROM AUTHOR]

• Both reinforcement groups retained extinction after post-retrieval extinction. • Both reinforcement groups recovered after standard extinction. • Greater recovery in high than low reinforcement group in standard extinction. • Post-acquisition threat ratings were higher in the 40% group than the 80% group. • Physiological arousal during memory reactivation predicted spontaneous recovery. Research has shown that a single presentation of the conditioned stimulus prior to extinction training can diminish conditioned responses. However, replication has proven difficult and appears to be limited by boundary conditions. Here we tested the boundary condition of memory strength by comparing the effect of reinforcement rate to assess its role in post-retrieval extinction. Eighty university students had undergone a three-day fear conditioning experiment in which two partial reinforcement schedules (40%, 80%) were applied. The findings indicated that both low and high partial reinforcement groups did not demonstrate recovery of conditioned responses after post-retrieval extinction. In contrast, both groups demonstrated significant recovery to standard extinction with significantly greater recovery in the 80% group relative to the 40% group. Additionally, we found that greater physiological arousal during memory retrieval significantly predicted recovery of fear at test phase. We conclude that when compared to a lower partial reinforcement schedule, a higher partial reinforcement resulted in the formation of a stronger memory as indicated by greater physiological arousal during memory reactivation and recovery of conditioned responses after standard extinction, but that it does not function as a boundary condition of post-retrieval extinction. These data are significant because it is the first study to investigate the effect of varying partial reinforcement schedules on fear recovery and add to the body of literature that continue to identify sources of failure in the application of post-retrieval extinction. [ABSTRACT FROM AUTHOR]

• Sleep deprivation directly after motor training impairs storage of memories. • Sleep deprivation directly after motor training also impairs retrieval of memories. • Sleeping longer directly following motor training facilitates memory formation. • Sleep may exert a subtle yet facilitatory role in consolidation of procedural memory. The relation between sleep and different forms of memory formation continues to be a relevant topic in our daily life. Sleep has been found to affect cerebellum-dependent procedural memory formation, but it remains to be elucidated to what extent the level of sleep deprivation directly after motor training also influences our ability to store and retrieve memories. Here, we studied the effect of disturbed sleep in mice during two different time-windows, one covering the first four hours following eyeblink conditioning (EBC) and another window following the next period of four hours. Compared to control mice with sleep ad libitum , the percentage of conditioned responses and their amplitude were impaired when mice were deprived of sleep directly after conditioning. This impairment was still significant when the learned EBC responses were extinguished and later reacquired. However, consolidation of eyeblink responses was not affected when mice were deprived later than four hours after acquisition, not even when tested during a different day-night cycle for control. Moreover, mice that slept longer directly following EBC showed a tendency for more conditioned responses. Our data indicate that consolidation of motor memories can benefit from sleep directly following memory formation. [ABSTRACT FROM AUTHOR]

• Synaptic plasticity may contribute to frequency and amplitude of conditioned responses. • Synaptic plasticity (LTD) does not explain timed conditioned Purkinje cell responses. • Intracellular temporal learning in Purkinje cells contribute to response timing. The general consensus for learning and memory, including in the cerebellum, is that modification of synaptic strength via long-term potentiation (LTP) or long-term depression (LTD) are the primary mechanisms for the formation of memories. Recent findings suggest additional cellular mechanisms – referred to as 'intrinsic plasticity' – where a neuron's membrane excitability intrinsically changes. These mechanisms act like a dimmer and alter neuronal responsiveness by adjusting response amplitudes and spike thresholds. Here, I argue that classical conditioning of cerebellar Purkinje cell responses reveals yet another cell-intrinsic learning mechanism which significantly differs from both changes in synaptic strength and changes in membrane excitability. When the conditional (CS) and unconditional stimuli (US) are delivered directly to the Purkinje cell's immediate pre-synaptic afferents, the parallel fibres and the climbing fibre, the cell learns to respond to the CS with a pause in its spontaneous firing that reflects the interval between the two stimuli. The pause response has a delayed onset and adaptively timed maximum, offset and duration, determined by the previously experienced CS-US interval. The timing is not dependent on any network-generated time-varying input. This implies the existence of a timing mechanism and a memory substrate that encodes the duration of the CS-US interval inside the Purkinje cell. Such temporal interval learning is not simply a change that causes more or less firing in response to an input. Here, I review these findings in relation to the standard theory of synaptic strength changes and the network interactions believed to be necessary for generating time codes. [ABSTRACT FROM AUTHOR]

Flavor evaluation is influenced by learning from experience with foods. One main influence is flavor-nutrient learning (FNL), a Pavlovian process whereby a flavor acts as a conditioned stimulus (CS) that becomes associated with the postingestive effects of ingested nutrients (the US). As a result that flavor becomes preferred and intake typically increases. This learning powerfully influences food choice and meal patterning. This paper summarizes how research elucidating the physiological and neural substrates of FNL has progressed in parallel with work characterizing how FNL affects perception, motivation, and behavior. The picture that emerges from this work is of a robust system of appetition (a term coined by Sclafani in contrast to the better-understood satiation signals) whereby ingested nutrients sensed in the gut evoke positive motivational responses. Appetition signals act within a meal to promote continued intake in immediate response to gut feedback, and act in the longer term to steer preference towards sensory cues that predict nutritional consequences. [ABSTRACT FROM AUTHOR]

Circadian rhythmic expression of conditioned place avoidance (CPA) was produced in Syrian hamsters homozygous for the circadian short period mutation, tau. In constant dim red light neither the 20 h endogenous period, nor a 20 h place conditioning schedule eliminated the 24 h modulation of CPA behavior described previously for wild type (wt) hamsters and other species. Tau mutants exhibited a 20 h rhythm superimposed on the 24 h modulation. The 20 h component was removed selectively with lesions of the suprachiasmatic nucleus. Wt animals conditioned on a 20 h schedule did not produce a 20 h rhythm, but still expressed the 24 h modulation. The results show that the context entrainable oscillator (CEO) underlying memory for the timing of an unconditioned stimulus, retains a period of about 24 h regardless of clock gene background (tau mutation) and/or the conditioning schedule (24 vs 20 h). Therefore the CEO responsible for time memory is distinct from the biological clock controlling activity; the underlying circadian molecular mechanisms may differ from the ubiquitous transcription-translation feedback oscillator; and time memory itself is not classically conditioned. [ABSTRACT FROM AUTHOR]