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Children are unique humans and experience varied development even though they are of the same gene or the same sex but grow and develop according to their respective characteristics. Of course, this condition also demands adjustments in providing appropriate and varied stimuli and responses. This study aims to observe the growth and development of children to explore the growth and development of children and see the reactions generated by children if given a specific stimulus. This research method uses longitudinal case studies. The respondents of this study were three children. The study found that children's cognitive, psychosocial and moral development can be developed by conditioning the child and the child's environment. Children's health and a conducive environment play an essential role in determining children's growth and development. Maternal health and parental cooperation also determine the growth and development of the child.

Defense industry is one of the sectors that boosts technological advancement and act as a trigger. In this industry, where personnel training plays a vital role, supporting military training with technology provides a great advantage on the battlefield. When we look at the problems that need to be solved, it is seen that the soldier's devotion to duty, his sense of absolute obedience and the soldier's need to be free from emotional depression. Recently, the masses have undergone intense migration movements due to the climate crisis, epidemics, hunger and wars. In this context, it seems that local people in the migrated region have a feeling of fear and hatred towards the newcomers. Mass media are the primary factors that cause this perception, called xenophobia. In this study, how perception management can be done through mass media and what the consequences may be will be discussed from a dystopian perspective and using the semiotic analysis method. As an example, through the images and dialogues in the "Men Against Fire" episode of the Black Mirror series, it will be examined how the soldier's motivation to become conditioned to the task during the training process is provided with technological support, and how effective the media can be in the context of perception management. As a result of the research, the outrage that xenophobic thought will cause in society, the dangers that arise in case of loss of control, and the role of the media in this process will be revealed and solution suggestions will be offered.

The educational technology designer should know about the learning theories to analyze the needs and design the contents in terms of the target that aimed to reach from learning operations. Educational technology is known as a process that includes many factors, which will provide a good simulation for the students. This research study used a basic qualitative study because it interprets an educational field experience. This is the type of research most commonly used in the fields of education, health, and social work because it is interpretative research. The participants in this study were two college instructors and 10 college students who volunteered to participate in this study. All participants have teaching experience and work in the same school. This study concludes that mixing instructional technology with behavioral theory provides an opportunity to stimulate students through psychological conditions by direct experiences and activities inside the classroom. Mixing instructional technology with constructivist theory allows educators to focus on how students can explore and discover class content and new experiences by explaining their mistakes, ideas, and experiences and the basics of the content.

Despite social changes and the opening up of all professions to men and women, society continues to adhere to many stereotypes, and many professions are still considered to be feminine or masculine. In addition to gendered representations of occupations, there are also social representations linked to the social prestige associated with a profession. These two elements shape the study and professional choices of individuals. Based on this observation, the aim of this article is twofold: I study individuals' perceptions of various professions and I analyse the influence of theses perceptions on their choice of orientation. I use a questionnaire administered to secondary school pupils and students. The results obtained show a differentiated influence of stereotypes on career plans. It also appears that individuals tend to underrate the professions they consider 'feminine'.

We evaluated two procedures to teach auditory-visual conditional discriminations (receptive labeling) to children with autism. The procedures evaluated a modified Structured Mix (SM) procedure and a modified Counterbalanced Random Rotation (RR) procedure. The modified SM procedure was based on the logic of simplifying the task by breaking it down into smaller, successive steps and by requiring mastery of each step before introducing the next. Compared to previous studies, the modified SM procedure contained fewer steps, less prompting, and a less stringent mastery criterion. The modified RR procedure targeted all three stimuli simultaneously by presenting them across consecutive trials, both during training and error correction. Sample stimuli were presented in a counterbalanced random order and the comparison stimuli were presented in counterbalanced random positions. Participants were nine children with autism. An adapted alternating treatments design was used. Results showed that the modified SM procedure was more efficient for four of the nine participants, the modified RR procedure was more efficient for one of the nine participants, both procedures were equally efficient for two participants, and neither procedure was effective for two of the nine participants. The modified SM procedure appeared more efficient than the SM procedure employed in previous studies. Despite results, further research is warranted to examine within subject comparisons between original discrimination training procedures and modified procedures.

This paper explores the role of material design as a form of institutional power within contemporary school settings. Drawing on concepts of "coercive design" and "hostile architecture" from design studies, the paper examines three "innovative" designs for classroom chairs -- relatively mundane but integral elements of the regulation and disciplining of school space. It is argued that the design intentions of these material objects reveal a number of constrained, conservative intentions to maintain the traditional ordered notion of the classroom as a place where students stay in their seats and engage in work. Tellingly, however, this corporeal manipulation and moderation is now couched in claims around desirable physiological and cognitive conditions for learning -- with students' bodies seen as objects to arrange and constrain in ways deemed conducive for learning. The paper problematises this de-socialised view of classrooms, alongside the underpinning sense of design solutionism and (mis)appropriation of "learning science" by product designers to justify their products' capacities to somehow cause learning to take place.

We assessed whether novel praise statements could be used to (a) maintain and increase responses with existing reinforcement histories and (b) teach a previously untaught response among children diagnosed with autism spectrum disorder across two experiments. During response-stimulus pairing, two responses resulted in preferred edibles but only one also produced a praise statement. In the absence of edibles, the response continuing to produce praise tended to persist more. Next, reversing the praise contingency tended to increase the other response. However, in no case did contingent delivery of those same praise statements result in the acquisition of untaught responses. These findings suggest that conditioning praise statements could serve different functions (antecedent or consequence) depending on the reinforcement history for particular responses.

Evidence for implicit aversive learning effects has been criticized for its lack of experimental rigor and statistical reliability. Here we examine whether attentional emotional responses to aversive conditioned stimuli can occur in the absence of stimulus-outcome contingency awareness, and use a novel Bayesian tool to reliably perform a post hoc categorization of awareness. Across two experiments (n = 40 and 69) participants completed an aversive conditioning task. A novel Bayesian awareness categorization tool was applied to sensitively measure contingency awareness. Finally, attentional and subjective responses toward conditioned stimuli were measured. For participants unaware of contingencies, conditioned stimuli generated attentional avoidance, but only aware participants showed subjective learning effects. For both experiments, awareness scores for unaware participants did not regress above chance level on a subsequent awareness check, revealing a reliable determination of unawareness states. These findings provide evidence for the existence of aversive learning in the absence of contingency awareness, as demonstrated via conditioned attentional responses, and build an analytical framework that can be extrapolated to other implicit paradigms.

Our preferences and evaluations are often affected by contextual factors. One unavoidable context is language. We used an evaluative conditioning (EC) paradigm (pairing neutral stimuli with emotional or neutral stimuli) to investigate whether our evaluations are equally conditioned in a first (L1) and a second language (L2). An EC effect was observed in both languages, however, if in L1 it occurred independently of recollection of the pairing of the stimuli, in second language memory seemed to play a larger role. These results were confirmed using a more implicit measure (memory confusion paradigm). Overall, the results suggest that conditioning occurs both in L1 and L2 but is weaker and more sensitive to memory of the emotional stimuli in L2. The study is the first demonstration that EC is modulated by language and converges with recent findings showing that linguistic context can modulate our behaviours.

To ensure the quality of training, skills developed and maintained, and expected standards for behavior analysts, several systems have been put into place across the years. Of these systems, perhaps the most widespread was the development of the Behavior Analyst Certification Board in 1998. Once all requirements are met, the final determinative step in obtaining certification is a multiple-choice examination. The use of a multiple-choice examination as the final determinative step in obtaining behavior analytic certification may create some concerns for behavior analysts. Identification of a positive correlation between the multiple-choice examination and performance may help ameliorate these concerns. The purpose of this study was to evaluate any potential correlations between scores on a popular commercially available prep examination and basic applied behavior analysis (ABA)--based autism intervention procedures with 25 professionals. Overall, the results indicated that multiple-choice examination scores were not significantly correlated with any assessments of performance.

Previous research on training auditory-visual conditional discriminations (AVCDs) have compared several prompt types including gestural, positional, and identity-matching prompts. Other prompting procedures, such as those that involve the manipulation of the comparison array, have received less attention in the applied literature. For example, the target response may be prompted by removing the negative comparisons (delayed prompting) or by replacing the negative comparisons with known targets (prompting by exclusion). Prompting by exclusion may be of particular interest as several studies have shown that exclusion-based performances may result in the nearly errorless transfer of stimulus control and the emergence of the speaker relation. The current study compared delayed prompting and prompting by exclusion procedures using a tablet-based arrangement on the acquisition of AVCDs for four children exhibiting language deficits. Both procedures were consistently effective and similarly efficient. Additional research is needed to determine the clinical utility of similar prompting arrangements, particularly with learners who may experience challenges during conditional discrimination training.

In the field of stimulus generalization, an old yet unresolved discussion pertains to what extent stimulus misidentifications contribute to the pattern of conditioned responding. In this article, we perform cluster analysis on six datasets (four published datasets and two unpublished datasets, included N = 950) to examine the relationship between interindividual differences in (a) stimulus identification, (b) patterns of generalized responding, and (c) verbalized generalization rules. The datasets were obtained from online predictive learning tasks where participants learned associations between colored cues and the presence or absence of a hypothetical outcome. In these datasets, stimulus identification and expectancy ratings were assessed in separate phases to a range of colors varying between blue-green. Using cluster analyses on performance during stimulus identification, we identified different subgroups of participants (good vs. bad identifiers). In all six datasets, we found a close relationship between the pattern of stimulus identification and the shape of the expectancy gradient across the test dimension between the identified subgroups. Furthermore, participants classified as good identifiers were more likely to report a similarity generalization rule than a relational or linear rule, suggesting that individual differences in stimulus identification are related to individual differences in generalization rules. These findings suggest that greater consideration should be given to interindividual variability in stimulus identification, inductive rules, and their relationship in explaining patterns of generalized responses.

Research relevant to Captology in education is in its infancy. Despite its relative newness, a dearth of literature exists on the subject that addresses the design of a persuasive game for educational purposes. Up to this point, the literature does not include any instructional design theories or theoretical frameworks that can be used specifically to design a persuasive game for educational use. This paper provides a theory-driven framework to guide instructional and game designers through the process of persuasive game design in education. The framework was developed based on multiple theories in learning, motivation, psychology, communication, as well as in other related disciplines. The framework covers the attitude-to-behavior process in designing persuasive games comprehensively: starting with strategies of designing a persuasive message and moving to principles of sending the message, which is followed by addressing the player's motivation, ability, cognition, and metacognition when receiving the message, and ending with the conditions that surround the player's behavior change due to the attitude. Research-based suggestions for the design of persuasive games for educational purposes are provided.

Instruction in auditory-visual conditional discriminations for young children with autism spectrum disorder is typically based on either a conditional-only or a simple-conditional method. In this study, we evaluated a modified simple-conditional method in which we removed the steps for which visual comparisons were presented in isolation. We compared this modified simple-conditional method with the conditional-only method when teaching auditory-visual conditional discriminations to six young Chinese children with autism spectrum disorder. We included two efficiency measures: total sessions and time to mastery. Our results replicated the findings of previous research in that both methods were efficacious for all but one participant. Although efficacy outcomes were similar across methods, the conditional-only method was more efficient across participants according to sessions and time to mastery. Thus, the results add to support for the use of the conditional-only method to teach auditory-visual conditional discriminations.

There are sex differences in anxiety disorders with regard to occurrence and severity of episodes such that females tend to experience more frequent and more severe episodes. Contextual fear learning and generalization are especially relevant to anxiety disorders, which are often defined by expressing fear and/or anxiety in safe contexts. In contextual fear conditioning, a representation of the context must first be created, and then that representation must be paired with an aversive consequence. With some variation, the experiments presented here use a 3-d procedure in which day 1 consists of pre-exposure to the to-be-shocked context, day 2 consists of a single context--shock pairing after some placement-to-shock interval (PSI), and day 3 consists of testing in either the same or a novel context. With shorter pre-exposure periods, male rats showed more contextual fear, consistent with previous literature; however, after longer pre-exposure periods, female rats showed greater contextual fear. Additionally, while pre-exposure and PSI are both periods of time prior to the shock, it was found that they were not equivalent to each other. Animals with 120 sec of pre-exposure and a 30-sec PSI show a differential level and time course of fear expression than animals who received no pre-exposure and a 150-sec PSI, and this further depended on sex of the rat. Additionally, an experiment comparing recently versus remotely acquired contextual fear was run. Males were again shown to have greater contextual fear at both time points, and this contextual fear incubated/increased over time in males but not females. To facilitate identification of what processes caused sex differences, we used BaconX, a conceptual and computational model of hippocampal contextual learning. Computational simulations using this model predicted many of our key findings. Furthermore, these simulations suggest potential mechanisms with regard to hippocampal computation; namely, an increased feature sampling rate in males, which may account for the sex differences presented here and in prior literature.

"The Oxford English Dictionary" defines fulfilment as 'satisfaction or happiness as a result of fully developing one's potential or realizing one's aspirations; self-fulfillment'. Not only has the idea of fulfilment underpinned 'approximately twenty centuries of philosophy' as Lefebvre notes, it plays an indispensable role in both popular and scholarly accounts of education and upbringing. Experiences of education, of upbringing and of 'life lessons', however, are so often "not" about the fulfilment of oneself, about the discovery and actualisation of one's full potential. Such experiences instead involve moments of sometimes irreparable failure and loss--a matter that has not received a great deal of attention in educational research and theory. After briefly examining the way that fulfilment is favourably framed both in humanistic psychology and in neo-humanist "Bildungstheorie," this paper considers some of the exceptions to the nearly ubiquitous identification of education with fulfilment: Arthur Schopenhauer's view of the irrationality of human (developmental) experience and Ludwig Wittgenstein's use of the term 'conditioning' ("Abrichtung") in some of his accounts of learning and socialisation. We then focus on failure and loss in education through an overview of the pedagogical theory of O.F. Bollnow. Bollnow, as is gradually being recognised in English-language scholarship, saw moments of uncertainty, disorientation and above all crisis as indispensable in educational experience--for both student and teacher. In this way, we show that instead of being the pursuit of self-fulfilment, education is unavoidably a matter of difficulty, disruption and also failure. It reshapes us, and this reshaping can be seen as being as much about formation as it is about deformation.

Local protein synthesis at synapses can provide a rapid supply of proteins to support synaptic changes during consolidation of new memories, but its role in the maintenance or updating of established memories is unknown. Consolidation requires new protein synthesis in the period immediately following learning, whereas established memories are resistant to protein synthesis inhibitors. We have previously reported that polyribosomes are up-regulated in the lateral amygdala (LA) during consolidation of aversive-cued Pavlovian conditioning. In this study, we used serial section electron microscopy reconstructions to determine whether the distribution of dendritic polyribosomes returns to baseline during the long-term memory phase. Relative to control groups, long-term memory was associated with up-regulation of polyribosomes throughout dendrites, including in dendritic spines of all sizes. Retrieval of a consolidated memory by presentation of a small number of cues induces a new, transient requirement for protein synthesis to maintain the memory, while presentation of a large number of cues results in extinction learning, forming a new memory. One hour after retrieval or extinction training, the distribution of dendritic polyribosomes was similar except in the smallest spines, which had more polyribosomes in the extinction group. Our results demonstrate that the effects of learning on dendritic polyribosomes are not restricted to the transient translation-dependent phase of memory formation. Cued Pavlovian conditioning induces persistent synapse strengthening in the LA that is not reversed by retrieval or extinction, and dendritic polyribosomes may therefore correlate generally with synapse strength as opposed to recent activity or transient translational processes.

Inclusion of male and female subjects in behavioral neuroscience research requires a concerted effort to characterize sex differences in standardized behavioral assays. Sex differences in hippocampus-dependent assays have been widely reported but are still poorly characterized. In the present study, we conducted a parametric analysis of spontaneous alternation, object recognition, and fear conditioning in a commonly used control strain, C57BL/6NTac. Our findings show largely similar performance between males and females across the majority of behavioral end points. However, we identified an important difference in nonassociative fear sensitization, whereby females showed an enhanced fear response to the 75-dB tone that is used as the conditional stimulus. In addition, we observed an impairment in object location performance in females that was ameliorated by more extensive habituation to handling. Together, these findings argue that sex differences in nonassociative fear responses to both novel auditory cues and novel objects need to be considered when designing and interpreting cognitive assays in C57BL/6 mice. Furthermore, this elevated fear sensitization could serve as a novel approach to model the increased incidence of anxiety disorders in women.

Recent data reveal that the thalamic nucleus reuniens (RE) has a critical role in the extinction of conditioned fear. Muscimol (MUS) infusions into the RE impair within-session extinction of conditioned freezing and result in poor long-term extinction memories in rats. Although this suggests that RE inactivation impairs extinction learning, it is also possible that it is involved in the consolidation of extinction memories. To examine this possibility, we examined the effects of RE inactivation on the consolidation and reconsolidation of fear extinction in male and female rats. Twenty-four hours after auditory fear conditioning, rats underwent an extinction procedure (45 CS-alone trials) in a novel context and were infused with saline (SAL) or MUS within minutes of the final extinction trial. Twenty-four hours later, conditioned freezing to the extinguished CS was assessed in the extinction context. Postextinction inactivation of the RE did not affect extinction retrieval. In a second experiment, rats underwent extinction training and, 24 h later, were presented with a single CS to reactivate the extinction memory; rats were infused with SAL or MUS immediately after the reactivation session. Pharmacological inactivation of the RE did not affect conditioned freezing measured in a drug-free retrieval test the following day. Importantly, we found in a subsequent test that MUS infusions immediately before retrieval testing increased conditioned freezing and impaired extinction retrieval, as we have previously reported. These results indicate that although RE inactivation impairs the expression of extinction, it does not impair either the consolidation or reconsolidation of extinction memories. We conclude that the RE may have a critical role in suppressing context-inappropriate fear memories in the extinction context.

Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage in a variety of both conditioned and unconditioned responses, the last several decades have seen the field narrow its focus to measure freezing as the sole indicator of conditioned fear. We previously reported that female rats were more likely than males to engage in darting, an escape-like conditioned response that is associated with heightened shock reactivity. To determine how experimental parameters contribute to the frequency of darting in both males and females, we manipulated factors such as chamber size, shock intensity, and number of trials. To better capture fear-related behavioral repertoires in our animals, we developed ScaredyRat, an open-source custom Python tool that analyzes Noldus Ethovision-generated raw data files to identify darters and quantify both conditioned and unconditioned responses. We found that, like freezing, conditioned darting occurrences scale with experimental alterations. While most darting occurs in females, we found that with an extended training protocol, darting can emerge in males as well. Collectively, our data suggest that darting reflects a behavioral switch in conditioned responding that is a product of an individual animal's sex, shock reactivity, and experimental parameters, underscoring the need for careful consideration of sex as a biological variable in classic learning paradigms.

Dopamine participates in encoding memories and could either encode rewarding/aversive value of unconditioned stimuli or act as a novelty signal triggering contextual learning. Here we show that intraperitoneal injection of the dopamine D1/5R antagonist SCH23390 impairs contextual fear conditioning and tone-shock association, while intrahippocampal injection only impairs contextual fear conditioning. By using the context pre-exposure facilitation effect test, we show that SCH23390 is able to block the encoding of the context during the pre-exposure phase. Thus, we provide additional evidence that dopamine is involved in encoding conjunctive representations of new contexts.

Child language acquisition research has provided ample evidence of lexical frequency effects. This corpus-based analysis introduces a novel frequency measure shown to significantly constrain adult language variation, but heretofore unexplored in child language acquisition research. Among adults, frequent occurrence of a form in a particular discourse context that conditions usage accumulates in memory over time and shapes the lexical representation of that form. This study contributes to the body of research on frequency effects in child language acquisition by testing whether such cumulative conditioning effects are also found among children, and, if so, at what age such effects appear. Specifically, the study investigates the influence of a distributional frequency measure (each verb form's likelihood of use in a switch vs same-reference discourse context) on variable subject personal pronoun (SPP) expression (N = 2227) in Spanish (e.g. "yo voy ~ voy," both meaning 'I go') in the speech of 65 monolingual children in two age cohorts. Results reveal sensitivity to the contextual conditioning of discourse continuity (switch reference) among both the younger (6- and 7-year-olds) and older (8- and 9-year-olds) children in support of previous research. In addition, each verb's likelihood of use in a switch-reference context significantly predicted the SPP use among the older children, but not the younger ones, suggesting that the cumulative effect of a probabilistic pattern takes time to emerge during childhood. The lexically specific accumulation in memory of contextual conditioning effects supports exemplar models of child language acquisition: each instance of use in discourse contributes to the lexical representation of that form and, over time, plays a role in the creation of morphosyntactic patterns during language development.

Fear generalization is one of the main symptoms of posttraumatic stress disorder. In rodents, the anterior cingulate cortex (ACC) and the hippocampus (HPC) control the expression of contextual fear memory generalization. Consistently, ACC projections to the ventral HPC contribute to contextual fear generalization. However, the roles of ACC projections to the dorsal HPC (dHPC) in fear generalization are unclear, although the dHPC is required for the retrieval of recent contextual fear memory. To investigate these roles, we examined the effects of optogenetic silencing and stimulation of these projections in contextual fear generalization at the recent and remote time points. Mice underwent contextual fear conditioning and, at 1 or 28 d later, were tested in the conditioned chamber, a novel context, or a similar context. Optogenetic activation of these projections induced higher freezing in mice in the novel context compared with the control group at a recent (1-d), but not remote (28-d), time point following conditioning, suggesting that activation of this pathway enhances contextual fear generalization. In contrast, optogenetic inactivation of these projections induced lower freezing in the similar context compared with the control group at a recent, but not remote, time point, suggesting that inactivation of this pathway impaired contextual fear generalization. These observations suggest that the ACC to the dHPC projections positively regulate the expression of contextual fear generalization when contextual fear memory is recent.

Evaluative conditioning (EC) refers to a change in liking of a conditioned stimulus (CS) consecutive to its repeated pairing with a valent unconditioned stimulus (US). We relied on a multinomial processing tree model to compare the processes underlying EC in middle-aged children (n = 57, M[subscript age] = 8.65, range = 6.94-11.03; 31 females) and young adults (n = 57, M[subscript age] = 19.16, range = 17.60-23.60; 53 females). We found that controllable and uncontrollable valence transfer processes concurrently contributed to EC in adults and provided initial evidence that they are already present in children. Moreover, the experiment revealed that both types of processes are weaker in children than in adults and that controllable processes are stronger in older children than in younger ones. These findings suggest that both controllable and uncontrollable processes already underlie EC in middle-aged children but that they continue to mature after childhood.

Fear is an adaptive emotion that serves to protect an organism against potential dangers. It is often studied using classical conditioning paradigms where a conditioned stimulus is paired with an aversive unconditioned stimulus to induce a threat response. Less commonly studied is a phenomenon that is related to this form of conditioning, known as latent inhibition. Latent inhibition (LI) is a paradigm in which a neutral cue is repeatedly presented in the absence of any aversive associations. Subsequent pairing of this pre-exposed cue with an aversive stimulus typically leads to reduced expression of a conditioned fear/threat response. In this article, we review some of the theoretical basis for LI and its behavioral and neural mechanisms. We compare and contrast LI and fear/threat extinction--a process in which a previously conditioned cue is repeatedly presented in the absence of aversive outcomes. We end with highlighting the potential clinical utility of LI. Particularly, we focus on how LI application could be useful for enhancing resilience, especially for individuals who are more prone to continuous exposure to trauma and stressful environments, such as healthcare workers and first responders. The knowledge to be gained from advancing our understanding of neural mechanisms in latent inhibition could be applicable across psychiatric disorders characterized by exaggerated fear responses and impaired emotion regulation.

The OECD's Programme for International Student Assessment (PISA) has become one of the key studies for evidence-based education policymaking across the globe. PISA has however received a lot of methodological criticism, including how the test scores are created. The aim of this paper is to investigate the so-called 'conditioning model', where background variables are used to derive student achievement scores, and the impact it has upon the PISA results. This includes varying the background variables used within the conditioning model and analysing its impact upon countries relatively positions in the PISA rankings. Our key finding is that the exact specification of the conditioning model matters; cross-country comparisons of PISA scores can change depending upon the statistical methodology used.

Damage to the hippocampus (HPC) typically causes retrograde amnesia for contextual fear conditioning. Repeating the conditioning over several sessions, however, can eliminate the retrograde amnesic effects. This form of reinstatement thus permits modifications to networks that can support context memory retrieval in the absence of the HPC. The present study aims to identify cortical regions that support the nonHPC context memory. Specifically, the contribution of the perirhinal cortex (PRH) and the anterior cingulate cortex (ACC) were examined because of their established importance to context memory. The findings show that context memories established through distributed reinstatement survive damage limited only to the HPC, PRH, or ACC. Combined lesions of the HPC and PRH, as well as the HPC and ACC, caused retrograde amnesia, suggesting that network modifications in the PRH and ACC enable context fear memories to become resistant to HPC damage.

The ability to generate memories that persist throughout a lifetime (that is, memory persistence) emerges in early development across species. Although it has been shown that persistent fear memories emerge between late infancy and adolescence in mice, it is unclear exactly when this transition takes place, and whether two major fear conditioning tasks, contextual and auditory fear, share the same time line of developmental onset. Here, we compared the ontogeny of remote contextual and auditory fear in C57BL/6J mice across early life. Mice at postnatal day (P)15, 21, 25, 28, and 30 underwent either contextual or auditory fear training and were tested for fear retrieval 1 or 30 d later. We found that mice displayed 30-d memory for context- and tone-fear starting at P25. We did not find sex differences in the ontogeny of either type of fear memory. Furthermore, 30-d contextual fear retrieval led to an increase in the number of c-Fos positive cells in the prelimbic region of the prefrontal cortex only at an age in which the contextual fear memory was successfully retrieved. These data delineate a precise time line for the emergence of persistent contextual and auditory fear memories in mice and suggest that the prelimbic cortex is only recruited for remote memory recall upon the onset of memory persistence.

It has been reported that during chemotherapy treatment, some patients can experience nausea before pharmacological administration, suggesting that contextual stimuli are associated with the nauseating effects. There are attempts to reproduce with animal models the conditions under which this phenomenon is observed to provide a useful paradigm for studying contextual aversion learning and the brain structures involved. This manuscript assessed the hippocampus involvement in acquiring and maintaining long-term conditioned place avoidance (CPA) induced by a gastric malaise-inducing agent, LiCl. Our results demonstrate that a reliable induction of CPA is possible after one acquisition trial. However, CPA establishment requires a 20-min confinement in the compartment associated with LiCl administration. Interestingly, both hippocampal regions seem to be necessary for CPA establishment; nonetheless, inactivation of the ventral hippocampus results in a reversion of avoidance and turns it into preference. Moreover, we demonstrate that activation of dorsal/ventral hippocampal NMDA receptors after CS-US association is required for long-term CPA memory maintenance.

Temporal association learning (TAL) allows for the linkage of distinct, nonsynchronous events across a period of time. This function is driven by neural interactions in the entorhinal cortical-hippocampal network, especially the neural input from the pyramidal cells in layer III of medial entorhinal cortex (MECIII) to hippocampal CA1 is crucial for TAL. Successful TAL depends on the strength of event stimuli and the duration of the temporal gap between events. Whereas it has been demonstrated that the neural input from pyramidal cells in layer II of MEC, referred to as Island cells, to inhibitory neurons in dorsal hippocampal CA1 controls TAL when the strength of event stimuli is weak, it remains unknown whether Island cells regulate TAL with long trace periods as well. To understand the role of Island cells in regulating the duration of the learnable trace period in TAL, we used Pavlovian trace fear conditioning (TFC) with a 60-sec long trace period (long trace fear conditioning [L-TFC]) coupled with optogenetic and chemogenetic neural activity manipulations as well as cell type-specific neural ablation. We found that ablation of Island cells in MECII partially increases L-TFC performance. Chemogenetic manipulation of Island cells causes differential effectiveness in Island cell activity and leads to a circuit imbalance that disrupts L-TFC. However, optogenetic terminal inhibition of Island cell input to dorsal hippocampal CA1 during the temporal association period allows for long trace intervals to be learned in TFC. These results demonstrate that Island cells have a critical role in regulating the duration of time bridgeable between associated events in TAL.

Strong evidence supports a role for protein degradation in fear memory formation. However, these data have been largely done in only male animals. Here, we found that following contextual fear conditioning, females, but not males, had increased levels of proteasome activity and K48 polyubiquitin protein targeting in the dorsal hippocampus, the latter of which occurred at chaperones or RNA processing proteins. In vivo CRISPR--dCas9-mediated repression of protein degradation in the dorsal hippocampus impaired contextual fear memory in females, but not males. These results suggest a sex-specific role for protein degradation in the hippocampus during the consolidation of a contextual fear memory.

An adaptive memory system should prioritize information surrounding a powerful learning event that may prove useful for predicting future meaningful events. The behavioral tagging hypothesis provides a mechanistic framework to interpret how weak experiences persist as durable memories through temporal association with a strong experience. Memories are composed of multiple elements, and different mnemonic aspects of the same experience may be uniquely affected by mechanisms that retroactively modulate a weakly encoded memory. Here, we investigated how emotional learning affects item and source memory for related events encoded close in time. Participants encoded trial-unique category exemplars before, during, and after Pavlovian fear conditioning. Selective retroactive enhancements in 24-h item memory were accompanied by a bias to misattribute items to the temporal context of fear conditioning. The strength of this source memory bias correlated with participants' retroactive item memory enhancement, and source misattribution to the emotional context predicted whether items were remembered overall. In the framework of behavioral tagging: Memory attribution was biased to the temporal context of the stronger event that provided the putative source of memory stabilization for the weaker event. We additionally found that fear conditioning selectively and retroactively enhanced stimulus typicality ratings for related items, and that stimulus typicality also predicted overall item memory. Collectively, these results provide new evidence that items related to emotional learning are misattributed to the temporal context of the emotional event and judged to be more representative of their semantic category. Both processes may facilitate memory retrieval for related events encoded close in time.

In conditioned odor aversion (COA), the association of a tasteless odorized solution (the conditioned stimulus [CS]) with an intraperitoneal injection of LiCl (the unconditioned stimulus [US]), which produces visceral malaise, results in its future avoidance. The strength of this associative memory is mainly dependent on two parameters, that is, the strength of the US and the interstimuli interval (ISI). In rats, COA has been observed only with ISIs of [less than or equal to] 15 min and LiCl (0.15 M) doses of 2.0% of bodyweight, when tested 48 h after acquisition (long-term memory [LTM]). However, we previously reported a robust aversion in rats trained with ISIs up to 60 min when tested 4 h after acquisition (short-term memory [STM]). Since memories get reactivated during retrieval, in the current study we hypothesized that testing for STM would reactivate this COA trace, strengthening its LTM. For this, we compared the LTM of rats trained with long ISIs or low doses of LiCl initially tested for STM with that of rats tested for LTM only. Interestingly, rats conditioned under parameters sufficient to produce STM, but not LTM, showed a reliable LTM when first tested for STM. These observations suggest that under suboptimal training conditions, such as long ISIs or low US intensities, a CS-US association is established but requires reactivation in the short-term in order to persist in the long-term.

Four experiments examined the effects of a dangerous context and a systemic epinephrine injection on sensory preconditioning in rats. In each experiment, rats were exposed to presentations of a tone and light in stage 1, light-shock pairings in stage 2, and test presentations of the tone alone and light alone in stage 3. Presentations of the tone and light in stage 1 occurred in either a safe or a previously shocked context, and/or under a systemic injection of epinephrine. Experiment 1 showed that a trace interval of 20 sec between presentations of the tone and light produced sensory preconditioning of the tone in a previously shocked context but not in a safe context, while experiment 2 provided evidence that this trace preconditioning was associative, due to the formation of a tone-light association. Experiment 3 showed that, in a safe context, exposure to the trace protocol under the influence of an epinephrine injection also produced sensory preconditioning of the tone, while experiment 4 provided evidence that a shocked context and an epinephrine injection have additive effects on trace preconditioning. These findings are discussed in relation to theories of trace conditioning. They suggest that the release of epinephrine by danger enhances attention and/or working memory processes, and thereby associative formation across a trace interval.

Dysfunctions in memory recall lead to pathological fear; a hallmark of trauma-related disorders, like posttraumatic stress disorder (PTSD). Both, heightened recall of an association between a cue and trauma, as well as impoverished recall that a previously trauma-related cue is no longer a threat, result in a debilitating fear toward the cue. Glucocorticoid-mediated action via the glucocorticoid receptor (GR) influences memory recall. This literature has primarily focused on GRs expressed in neurons or ignored cell-type specific contributions. To ask how GR action in nonneuronal cells influences memory recall, we combined auditory fear conditioning in mice and the knockout of GRs in astrocytes in the prefrontal cortex (PFC), a brain region implicated in memory recall. We found that knocking out GRs in astrocytes of the PFC disrupted memory recall. Specifically, we found that knocking out GRs in astrocytes in the PFC (AstroGRKO) after fear conditioning resulted in higher levels of freezing to the CS+ tone when compared with controls (AstroGRintact). While we did not find any differences in extinction of fear toward the CS+ between these groups, AstroGRKO female but not male mice showed impaired recall of extinction training. These results suggest that GRs in cortical astrocytes contribute to memory recall. These data demonstrate the need to examine GR action in cortical astrocytes to elucidate the basic neurobiology underlying memory recall and potential mechanisms that underlie female-specific biases in the incidence of PTSD.

The effect of repetitive training on learned behavior has been an important subject in neuroscience. In instrumental conditioning in mammals, learned action early in training is often goal-driven and controlled by outcome expectancy, but as training progresses, it becomes more habitual and insensitive to outcome devaluation. Similarly, we recently showed in Pavlovian conditioning in crickets ("Gryllus bimaculatus") that a conditioned response (CR) is initially sensitive to devaluation of the unconditioned stimulus but becomes insensitive to it after extended training. It is known that habitual responses after extended instrumental training are characterized by a higher context specificity than are initial goal-directed actions in mammals. In this study, we investigated whether this is applicable to Pavlovian conditioning in crickets. In crickets that received a standard amount of training to associate an odor with water reward under illumination, CR under illumination was stronger than that in the dark. In crickets that received extended training under illumination, on the other hand, the level of CR did not differ in different light conditions. Further experiments confirmed that context specificity decreases with the development of behavioral automaticity by extended training, as opposed to findings in instrumental training in mammals. We conclude that the nature of habitual behaviors after extended training differs in different learning systems of animals.

The efficacy of pharmacological disruption of fear memory reconsolidation depends on several factors, including memory strength and age. We built on previous observations that systemic treatment with the nootropic nefiracetam potentiates cued fear memory destabilization to facilitate mifepristone-induced reconsolidation impairment. Here, we applied nefiratecam and mifepristone to strongly conditioned, 1-wk-old contextual fear memories in male rats. Unexpectedly, the combined treatment did not result in impairment of contextual fear expression. However, mifepristone did reduce freezing to a novel context. These observations suggest that strong and established contextual fear memories do undergo destabilization without the need for pharmacological facilitation, and that impairments in strong context fear memory reconsolidation can manifest as a reduction in generalization.

While interest in active avoidance has recently been resurgent, many concerns relating to the nature of this form of learning remain unresolved. By separating stimulus and response acquisition, aversive Pavlovian-instrumental transfer can be used to measure the effect of avoidance learning on threat processing with more control than typical avoidance procedures. However, the motivational substrates that contribute to the aversive transfer effect have not been thoroughly examined. In three studies using rodents, the impact of a variety of aversive signals on shock-avoidance responding (i.e., two-way shuttling) was evaluated. Fox urine, as well as a tone paired with the delivery of the predator odor were insufficient modulatory stimuli for the avoidance response. Similarly, a signal for the absence of food did not generate appropriate aversive motivation to enhance shuttling. Only conditioned Pavlovian stimuli that had been paired with unconditioned threats were capable of augmenting shock-avoidance responding. This was true whether the signaled outcome was the same (e.g., shock) or different (e.g., klaxon) from the avoidance outcome (i.e., shock). These findings help to characterize the aversive transfer effect and provide a more thorough analysis of its generalization to warning signals for different kinds of threats. This feature of aversive motivation has not been demonstrated using conventional avoidance procedures and could be potentially useful for applying avoidance in treatment settings.

Fear can potently inhibit ongoing behavior, including reward-seeking, yet the neural circuits that underlie such suppression remain to be clarified. Prior studies have demonstrated that distinct subregions of the rodent medial prefrontal cortex (mPFC) differentially affect fear behavior, whereby fear expression is promoted by the more dorsal prelimbic cortex (PL) and inhibited by the more ventral infralimbic cortex (IL). These mPFC regions project to subregions of the nucleus accumbens, the core (NAcC) and shell (NAcS), that differentially contribute to reward-seeking as well as affective processes that may be relevant to fear expression. Here, we investigated how these mPFC and NAc subregions contribute to discriminative fear conditioning, assessed by conditioned suppression of reward-seeking. Bilateral inactivation of the NAcS or PL reduced the expression of conditioned suppression to a shock-associated CS+, whereas NAcC inactivation reduced reward-seeking without affecting suppression. IL inactivation caused a general reduction in conditioned suppression following discriminative conditioning, but not when using a single-stimulus design. Pharmacological disconnection of the PL [right arrow] NAcS pathway revealed that this projection mediates conditioned suppression. These data add to a growing literature implicating discrete cortico-striatal pathways in the suppression of reward-seeking in response to aversive stimuli. Dysfunction within related structures may contribute to aberrant patterns of behavior in psychiatric illnesses including substance use disorders.

Reduction in the expression or function of [alpha]5-subunit-containing GABA[subscript A] receptors ([alpha]5GABA[subscript A]Rs) leads to improvement in several hippocampus-dependent memory domains. However, studies thus far mostly lack anatomical specificity in terms of neuronal circuits and populations. We demonstrate that mice with a selective knockdown of [alpha]5GABA[subscript A]Rs in CA1 pyramidal neurons ([alpha]5CA1KO mice) show improved spatial and trace fear-conditioning memory. Unexpectedly, [alpha]5CA1KO mice were comparable to controls in contextual fear-conditioning but showed an impairment in context discrimination, suggesting fine-tuning of activity in CA1 pyramidal cell dendrites through [alpha]5-mediated inhibition might be necessary for distinguishing highly similar contexts.

Memory deficits significantly decrease an individual's quality of life and are a pervasive comorbidity of epilepsy. Despite the various distinct processes of memory, the majority of epilepsy research has focused on seizures during the encoding phase of memory, therefore the effects of a seizure on other memory processes is relatively unknown. In the present study, we investigated how a single seizure affects memory reactivation in C57BL/6J adult mice using an associative conditioning paradigm. Initially, mice were trained to associate a tone (conditioned stimulus), with the presence of a shock (unconditioned stimulus). Flurothyl was then administered 1 h before, 1 h after, or 6 h before a memory reactivation trial. The learned association was then assessed by presenting a conditioned stimulus in a new context 24 h or 1 wk after memory reactivation. We found that mice receiving a seizure 1 h prior to reactivation exhibited a deficit in memory 24 h later but not 1 wk later. When mice were administered a seizure 6 h before or 1 h after reactivation, there were no differences in memory between seizure and control animals. Altogether, our study indicates that an acute seizure during memory reactivation leads to a temporary deficit in associative memory in adult mice. These findings suggest that the cognitive impact of a seizure may depend on the timing of the seizure relative to the memory process that is active.

Learning and memory involves a large neural network of many brain regions, including the notable hippocampus along with the retrosplenial cortex (RSC) and lateral septum (LS). Previous studies have established that the dorsal hippocampus (dHPC) plays a critical role during the acquisition and retrieval/expression of episodic memories. However, the role of downstream circuitry from the dHPC, including the dHPC-to-RSC and dHPC-to-LS pathways, has come under scrutiny only recently. Here, we used an optogenetic approach with contextual fear conditioning in mice to determine whether the above two pathways are involved in acquisition and expression of contextual fear memory. We found that a selective inhibition of the dHPC neuronal terminals in either the RSC or LS during acquisition impaired subsequent memory performance, suggesting that both the dHPC-to-RSC and dHPC-to-LS pathways play a critical role in memory acquisition. We also selectively inhibited the two dHPC efferent pathways during memory retrieval and found a differential effect on memory performance. These results indicate the intricacies of memory processing and that hippocampal efferents to cortical and subcortical regions may be differentially involved in aspects of physiological and cognitive memory processes.

Reconsolidation is a time-limited process under which reactivated memory content can be modified. Works focused on studying reconsolidation mainly restrict intervention to the moments immediately after reactivation and to recently acquired memories. However, the brain areas activated during memory retrieval depend on when it was acquired, and it is relatively unknown how different brain sites contribute to reconsolidation and persistence of reactivated recent and remote fear memories. Here, we sought to investigate the participation of prelimbic (PL) and anterior cingulate cortices (ACC) in recent (1 d old) and remote (21 d old) fear memory reconsolidation and persistence. Male Wistar rats were submitted to the contextual fear conditioning protocol. Tamoxifen (TMX), an estrogen receptor modulator known to inhibit protein kinase C activity was used to interfere with these processes. When infused into the PL cortex, but not into the ACC, TMX administration immediately or 6 h after recent fear memory reactivation impaired memory reconsolidation and persistence, respectively. TMX administered immediately after remote memory reactivation impaired memory reconsolidation when infused into the PL cortex and ACC. However, remote memory persistence was only affected when TMX was infused 6 h after memory reactivation into the ACC and no effect was observed when TMX was infused 6 h after memory reactivation into PL cortex. Together, the findings provide further evidence on the participation of PL cortex and ACC in reconsolidation of recent and remote fear memories and suggest that the persistence of a reactivated fear memory becomes independent on the PL cortex with memory age and dependent on the ACC.

Chronic stress typically leads to deficits in fear extinction when tested soon after chronic stress ends. Given the importance of extinction in updating fear memories, the current study examined whether fear extinction was impaired in rats that were chronically stressed and then given a break from the end of chronic stress to the start of fear conditioning and extinction. Male rats were chronically stressed by restraint (6 h/d/21 d) and tested soon (termed immediate, STR-IMM), or 3 or 6 wk after a rest period from restraint (termed rest or "R," STR-R3, STR-R6). In Experiment 1, STR-R3 and STR-R6 discriminated between the cue and nonshock context better than STR-IMM or control. Interestingly, STR-IMM showed high freezing to the nonshock context. Consequently, Experiment 2 investigated whether STR-IMM generalized across contexts, which was not supported. Experiment 3 determined whether STR-IMM were susceptible to second-order conditioning to a novel context, but showed that the level of second-order conditioning was similar for all groups. These findings reveal that rats exposed to chronic stress and then given a rest period of 3 or 6 wk, express unique fear extinction profiles compared to control and STR-IMM. Specifically, STR-R demonstrated excellent cue and context discrimination during extinction, and perhaps showed a stress inoculation effect. For STR-IMM, the heightened freezing under these extensive acclimation parameters was not attributed to generalization nor to second-order fear conditioning to "safe" contexts and, instead, may reflect hypervigilance.

In signaled active avoidance (SigAA), rats learn to suppress Pavlovian freezing and emit actions to remove threats and prevent footshocks. SigAA is critical for understanding aversively motivated instrumental behavior and anxiety-related active coping. However, with standard protocols ~25% of rats exhibit high freezing and poor avoidance. This has dampened enthusiasm for the paradigm and stalled progress. We demonstrate that reducing shock imminence with long-duration warning signals leads to greater freezing suppression and perfect avoidance in all subjects. This suggests that instrumental SigAA mechanisms evolved to cope with distant harm and protocols that promote inflexible Pavlovian reactions are poorly designed to study avoidance.

In evaluative conditioning, if one shape (conditional stimulus [CS]; CSp) is paired with pleasant unconditional stimulus (US) images and another (CSu) is paired with unpleasant US images differential CS valence and US expectancy develops, such that participants evaluate the CSp as more pleasant and more predictive of pleasant images than the CSu. This conditional CS valence and US expectancy can be reduced in an extinction procedure in which the CSs are repeatedly presented alone. We investigated whether evaluative and expectancy learning is subject to relapse (spontaneous recovery, reinstatement, and renewal) after extinction in a picture-picture evaluative conditioning paradigm. In Stream 1, after acquisition and extinction, the spontaneous recovery test was completed after a delay. During the spontaneous recovery test, conditional expectancy learning, but not conditional evaluative learning, returned. In Stream 2, the US pictures were presented in a random stream after extinction (reinstatement manipulation) which led to the return of conditional evaluative and expectancy learning. In Stream 3, after acquisition training in Context A and extinction training in Context B, conditional expectancy and evaluative learning returned when participants completed the renewal test in the acquisition context (Context A; ABA renewal). Overall, the results suggest that conditional evaluative learning is subject to reinstatement and renewal, but not to spontaneous recovery, in a picture-picture evaluative conditioning paradigm.

The evaluative conditioning (EC) phenomenon is central to the study of preference acquisition and attitude formation. Early studies have reported EC in the absence of awareness, but more recent work has questioned this conclusion. In previous work, using briefly presented and pattern-masked conditioned stimuli (CSs), we found that above-chance forced-choice identification of CSs is necessary for EC. Here we extend this work by addressing more directly the inherently subjective issue of consciousness. In 2 studies, we assessed whether above-threshold perceptual awareness of CSs is necessary for EC. Contrasting unconscious learning claims, EC was absent under low and intermediate levels of perceptual awareness. Additional findings suggest that the perceptual awareness task does not interfere with EC, and that it is more sensitive than memory-based awareness proxies. We also found that a confounded variant of the forced-choice identification task can artifactually induce EC; and that an unconfounded version of the task does not induce nor interfere with EC. We discuss limitations of the present studies as well as their relevance for the debate about the automaticity of evaluative learning.