RESUMEN
Pavlovian fear conditioning is a particularly useful behavioral paradigm for exploring the molecular mechanisms of learning and memory because a well-defined response to a specific environmental stimulus is produced through associative learning processes. Synaptic plasticity in the lateral nucleus of the amygdala (LA) underlies this form of associative learning. Here, we summarize the molecular mechanisms that contribute to this synaptic plasticity in the context of auditory fear conditioning, the form of fear conditioning best understood at the molecular level. We discuss the neurotransmitter systems and signaling cascades that contribute to three phases of auditory fear conditioning: acquisition, consolidation, and reconsolidation. These studies suggest that multiple intracellular signaling pathways, including those triggered by activation of Hebbian processes and neuromodulatory receptors, interact to produce neural plasticity in the LA and behavioral fear conditioning. Collectively, this body of research illustrates the power of fear conditioning as a model system for characterizing the mechanisms of learning and memory in mammals and potentially for understanding fear-related disorders, such as PTSD and phobias.
Asunto(s)
Encéfalo/metabolismo , Miedo , Aprendizaje , Memoria , Transducción de Señal , Animales , Condicionamiento Psicológico , Humanos , RatasRESUMEN
Neural plasticity in subareas of the rodent amygdala is widely known to be essential for Pavlovian threat conditioning and safety learning. However, less consistent results have been observed in human neuroimaging studies. Here, we identify and test three important factors that may contribute to these discrepancies: the temporal profile of amygdala response in threat conditioning, the anatomical specificity of amygdala responses during threat conditioning and safety learning, and insufficient power to identify these responses. We combined data across multiple studies using a well-validated human threat conditioning paradigm to examine amygdala involvement during threat conditioning and safety learning. In 601 humans, we show that two amygdala subregions tracked the conditioned stimulus with aversive shock during early conditioning while only one demonstrated delayed responding to a stimulus not paired with shock. Our findings identify cross-species similarities in temporal- and anatomical-specific amygdala contributions to threat and safety learning, affirm human amygdala involvement in associative learning and highlight important factors for future associative learning research in humans.
Asunto(s)
Amígdala del Cerebelo , Condicionamiento Clásico , Miedo , Amígdala del Cerebelo/fisiología , Condicionamiento Clásico/fisiología , Miedo/fisiología , Humanos , Plasticidad NeuronalRESUMEN
Information about dangers can spread effectively by observation of others' threat responses. Yet, it is unclear if such observational threat information interacts with associative memories that are shaped by the individual's direct, firsthand experiences. Here, we show in humans and rats that the mere observation of a conspecific's threat reactions reinstates previously learned and extinguished threat responses in the observer. In two experiments, human participants displayed elevated physiological responses to threat-conditioned cues after observational reinstatement in a context-specific manner. The elevation of physiological responses (arousal) was further specific to the context that was observed as dangerous. An analogous experiment in rats provided converging results by demonstrating reinstatement of defensive behavior after observing another rat's threat reactions. Taken together, our findings provide cross-species evidence that observation of others' threat reactions can recover associations previously shaped by direct, firsthand aversive experiences. Our study offers a perspective on how retrieval of threat memories draws from associative mechanisms that might underlie both observations of others' and firsthand experiences.
Asunto(s)
Condicionamiento Clásico/fisiología , Miedo/psicología , Generalización Psicológica/fisiología , Conducta Imitativa/fisiología , Aprendizaje Social/fisiología , Animales , Nivel de Alerta , Electrochoque , Femenino , Humanos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
When patients seek professional help for mental disorders, they often do so because of troubling subjective affective experiences. While these subjective states are at the center of the patient's symptomatology, scientific tools for studying them and their cognitive antecedents are limited. Here, we explore the use of concepts and analytic tools from the science of consciousness, a field of research that has faced similar challenges in having to develop robust empirical methods for addressing a phenomenon that has been considered difficult to pin down experimentally. One important strand is the operationalization of some relevant processes in terms of metacognition and confidence ratings, which can be rigorously studied in both humans and animals. By assessing subjective experience with similar approaches, we hope to develop new scientific approaches for studying affective processes and promoting psychological resilience in the face of debilitating emotional experiences.
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Metacognición , Humanos , Metacognición/fisiología , Afecto/fisiología , Estado de Conciencia/fisiología , Animales , Emociones/fisiologíaRESUMEN
Mental health problems often involve clusters of symptoms that include subjective (conscious) experiences as well as behavioral and/or physiological responses. Because the bodily responses are readily measured objectively, these have come to be emphasized when developing treatments and assessing their effectiveness. On the other hand, the subjective experience of the patient reported during a clinical interview is often viewed as a weak correlate of psychopathology. To the extent that subjective symptoms are related to the underlying problem, it is often assumed that they will be taken care of if the more objective behavioral and physiological symptoms are properly treated. Decades of research on anxiety disorders, however, show that behavioral and physiological symptoms do not correlate as strongly with subjective experiences as is typically assumed. Further, the treatments developed using more objective symptoms as a marker of psychopathology have mostly been disappointing in effectiveness. Given that "mental" disorders are named for, and defined by, their subjective mental qualities, it is perhaps not surprising, in retrospect, that treatments that have sidelined mental qualities have not been especially effective. These negative attitudes about subjective experience took root in psychiatry and allied fields decades ago when there were few avenues for scientifically studying subjective experience. Today, however, cognitive neuroscience research on consciousness is thriving, and offers a viable and novel scientific approach that could help achieve a deeper understanding of mental disorders and their treatment.
Asunto(s)
Trastornos Mentales , Ansiedad , Trastornos de Ansiedad , Miedo , Humanos , Trastornos Mentales/terapia , PsicopatologíaRESUMEN
Consciousness is currently a thriving area of research in psychology and neuroscience. While this is often attributed to events that took place in the early 1990s, consciousness studies today are a continuation of research that started in the late 19th century and that continued throughout the 20th century. From the beginning, the effort built on studies of animals to reveal basic principles of brain organization and function, and of human patients to gain clues about consciousness itself. Particularly important and our focus here is research in the 1950s, 1960s, and 1970s involving three groups of patients-amnesia, split brain, and blindsight. Across all three groups, a similar pattern of results was found-the patients could respond appropriately to stimuli that they denied seeing (or in the case of amnesiacs, having seen before). These studies paved the way for the current wave of research on consciousness. The field is, in fact, still grappling with the implications of the findings showing that the ability to consciously know and report the identity of a visual stimulus can be dissociated in the brain from the mechanisms that underlie the ability to behave in a meaningful way to the same stimulus.
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Estado de Conciencia , Neurociencias/historia , Psicología/historia , Animales , Conducta/fisiología , Encéfalo/fisiología , Historia del Siglo XIX , Historia del Siglo XX , HumanosRESUMEN
Norepinephrine (NE) plays a central role in the acquisition of aversive learning via actions in the lateral nucleus of the amygdala (LA) [1, 2]. However, the function of NE in expression of aversively-conditioned responses has not been established. Given the role of the central nucleus of the amygdala (CeA) in the expression of such behaviors [3-5], and the presence of NE axons projections in this brain nucleus [6], we assessed the effects of NE activity in the CeA on behavioral expression using receptor-specific pharmacology and cell- and projection-specific chemogenetic manipulations. We found that inhibition and activation of locus coeruleus (LC) neurons decreases and increases freezing to aversively conditioned cues, respectively. We then show that locally inhibiting or activating LC terminals in CeA is sufficient to achieve this bidirectional modulation of defensive reactions. These findings support the hypothesis that LC projections to CeA are critical for the expression of defensive responses elicited by conditioned threats.
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Reacción de Prevención/fisiología , Núcleo Amigdalino Central/fisiología , Norepinefrina/fisiología , Animales , Complejo Nuclear Basolateral/fisiología , Tronco Encefálico/fisiología , Condicionamiento Clásico/fisiología , Miedo/fisiología , Locus Coeruleus/metabolismo , Masculino , Neuronas/metabolismo , Norepinefrina/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
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.
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Reacción de Prevención , Generalización Psicológica , Motivación , Estimulación Acústica , Animales , Condicionamiento Clásico , Electrochoque , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
While our understanding of appetitive motivation has benefited immensely from the use of selective outcome devaluation tools, the same cannot be said about aversive motivation. Findings from appetitive conditioning studies have shown that basal amygdala is required for behaviors that are sensitive to updates in outcome value, but similar results in aversive motivation are difficult to interpret due to a lack of outcome specificity. The studies reported here sought to develop procedures to isolate sensory-specific processes in aversive learning and behavior and to assess the possible contribution of the basal amygdala. Post-training changes to outcome value produced commensurate changes to subsequently tested conditioned responding in male rodents. Specifically, increases in shock intensity (i.e., inflation) augmented, while repeated exposure to (i.e., habituation of) an aversive sound (klaxon-horn) reduced freezing to conditioned stimuli previously paired with these outcomes. This was extended to a discriminative procedure, in which following revaluation of one event, but not the other, responding was found to be dependent on outcome value signaled by each cue. Chemogenetic inactivation of basal amygdala impaired this discrimination between stimuli signaling differently valued outcomes, but did not affect the revaluation process itself. These findings demonstrate a contribution of the basal amygdala to aversive outcome-dependent motivational processes.SIGNIFICANCE STATEMENT The specific content of pavlovian associative learning has been well studied in appetitive motivation, where the value of different foods can be easily manipulated. This has facilitated our understanding of the neural circuits that generate different forms of motivation (i.e., sensory specific vs general). Studies of aversive learning have not produced the same degree of understanding with regard to sensory specificity due to a lack of tools for evaluating sensory-specific processes. Here we use a variant of outcome devaluation procedures with aversive stimuli to study the role of basal amygdala in discriminating between aversive stimuli conveying different degrees of threat. These findings have implications for how we study generalized threat to identify dysregulation that can contribute to generalized anxiety.
Asunto(s)
Amígdala del Cerebelo/fisiología , Aprendizaje por Asociación/fisiología , Miedo/fisiología , Reacción Cataléptica de Congelación/fisiología , Animales , Condicionamiento Clásico/fisiología , Masculino , Motivación/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
Emotional states of consciousness, or what are typically called emotional feelings, are traditionally viewed as being innately programmed in subcortical areas of the brain, and are often treated as different from cognitive states of consciousness, such as those related to the perception of external stimuli. We argue that conscious experiences, regardless of their content, arise from one system in the brain. In this view, what differs in emotional and nonemotional states are the kinds of inputs that are processed by a general cortical network of cognition, a network essential for conscious experiences. Although subcortical circuits are not directly responsible for conscious feelings, they provide nonconscious inputs that coalesce with other kinds of neural signals in the cognitive assembly of conscious emotional experiences. In building the case for this proposal, we defend a modified version of what is known as the higher-order theory of consciousness.
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Amígdala del Cerebelo/fisiología , Cognición/fisiología , Estado de Conciencia/fisiología , Miedo/fisiología , Amígdala del Cerebelo/anatomía & histología , Concienciación/fisiología , Miedo/psicología , Humanos , Memoria a Corto Plazo/fisiología , Corteza Visual/anatomía & histología , Corteza Visual/fisiologíaRESUMEN
Signaled active avoidance (SigAA) is the key experimental procedure for studying the acquisition of instrumental responses toward conditioned threat cues. Traditional analytic approaches (e.g., general linear model) often obfuscate important individual differences, although individual differences in learned responses characterize both animal and human learning data. However, individual differences models (e.g., latent growth curve modeling) typically require large samples and onerous computational methods. Here, we present an analytic methodology that enables the detection of individual differences in SigAA performance at a high accuracy, even when a single animal is included in the data set (i.e., n = 1 level). We further show an online software that enables the easy application of our method to any SigAA data set.
Asunto(s)
Reacción de Prevención , Individualidad , Modelos Estadísticos , Pruebas Psicológicas , Programas Informáticos , Animales , Condicionamiento Psicológico , Interpretación Estadística de Datos , Masculino , Ratas Sprague-Dawley , Tiempo de Reacción , Reproducibilidad de los ResultadosRESUMEN
Patients with anxiety disorders often experience a relapse in symptoms after exposure therapy. Similarly, threat responses acquired during Pavlovian threat conditioning often return after extinction learning. Accordingly, there is a need for alternative methods to persistently reduce threat responding. Studies in rodents have suggested that exercising behavioral control over an aversive stimulus can persistently diminish threat responses, and that these effects are mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this fMRI study, we attempted to translate these findings to humans. Subjects first underwent threat conditioning. We then contrasted two forms of safety learning: active avoidance, in which participants could prevent the shock through an action, and yoked extinction, with shock presentation matched to the active condition, but without instrumental control. The following day, we assessed subjects' threat responses (measured by skin conductance) to the conditioned stimuli without shock. Subjects next underwent threat conditioning with novel stimuli. Yoked extinction subjects showed an increase in conditioned response to stimuli from the previous day, but the active avoidance group did not. Additionally, active avoidance subjects showed reduced conditioned responding during novel threat conditioning, but the extinction group did not. We observed between-group differences in striatal BOLD responses to shock omission in Avoidance/Extinction. These findings suggest a differential role for the striatum in human active avoidance versus extinction learning, and indicate that active avoidance may be more effective than extinction in persistently diminishing threat responses.SIGNIFICANCE STATEMENT Extinguished threat responses often reemerge with time, highlighting the importance of identifying more enduring means of attenuation. We compared the effects of active avoidance learning and yoked extinction on threat responses in humans and contrasted the neural circuitry engaged by these two processes. Subjects who learned to prevent a shock through an action maintained low threat responses after safety learning and showed attenuated threat conditioning with novel stimuli, in contrast to those who underwent yoked extinction. The results suggest that experiences of active control over threat engage the striatum and promote a shift from expression of innate defensive responses toward more adaptive behavioral responses to threatening stimuli.
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Atención/fisiología , Reacción de Prevención/fisiología , Condicionamiento Clásico/fisiología , Cuerpo Estriado/fisiología , Extinción Psicológica/fisiología , Red Nerviosa/fisiología , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Translation in dendrites is believed to support synaptic changes during memory consolidation. Although translational control mechanisms are fundamental mediators of memory, little is known about their role in local translation. We previously found that polyribosomes accumulate in dendritic spines of the adult rat lateral amygdala (LA) during consolidation of aversive pavlovian conditioning and that this memory requires cap-dependent initiation, a primary point of translational control in eukaryotic cells. Here we used serial electron microscopy reconstructions to quantify polyribosomes in LA dendrites when consolidation was blocked by the cap-dependent initiation inhibitor 4EGI-1. We found that 4EGI-1 depleted polyribosomes in dendritic shafts and selectively prevented their upregulation in spine heads, but not bases and necks, during consolidation. Cap-independent upregulation was specific to spines with small, astrocyte-associated synapses. Our results reveal that cap-dependent initiation is involved in local translation during learning and that local translational control varies with synapse type.SIGNIFICANCE STATEMENT Translation initiation is a central regulator of long-term memory formation. Local translation in dendrites supports memory by providing necessary proteins at synaptic sites, but it is unknown whether this requires initiation or bypasses it. We used serial electron microscopy reconstructions to examine polyribosomes in dendrites when memory formation was blocked by an inhibitor of translation initiation. This revealed two major pools of polyribosomes that were upregulated during memory formation: one pool in dendritic spine heads that was initiation dependent and another pool in the bases and necks of small spines that was initiation independent. Thus, translation regulation differs between spine types and locations, and translation that occurs closest to individual synapses during memory formation is initiation dependent.
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Complejo Nuclear Basolateral/citología , Espinas Dendríticas/metabolismo , Regulación de la Expresión Génica/fisiología , Consolidación de la Memoria/fisiología , Neuronas/ultraestructura , Biosíntesis de Proteínas/fisiología , Análisis de Varianza , Animales , Aprendizaje por Asociación/efectos de los fármacos , Aprendizaje por Asociación/fisiología , Complejo Nuclear Basolateral/diagnóstico por imagen , Complejo Nuclear Basolateral/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Clásico/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Hidrazonas/farmacología , Procesamiento de Imagen Asistido por Computador , Masculino , Consolidación de la Memoria/efectos de los fármacos , Microscopía Electrónica de Transmisión , Modelos Animales , Neuroimagen , Neuronas/efectos de los fármacos , Polirribosomas/efectos de los fármacos , Polirribosomas/ultraestructura , Biosíntesis de Proteínas/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Sinapsis/ultraestructura , Tiazoles/farmacologíaRESUMEN
Noradrenergic signaling in the amygdala is important for processing threats and other emotionally salient stimuli, and ß-adrenergic receptor activation is known to enhance neuronal spiking in the lateral amygdala (LA) of juvenile animals. Nevertheless, intracellular recordings have not yet been conducted to determine the effect of ß-adrenergic receptor activation on spike properties in the adult LA, despite the potential significance of developmental changes between adolescence and adulthood. Here we demonstrate that the ß-adrenergic agonist isoproterenol (15 µM) enhances spike frequency in dorsal LA principal neurons of juvenile male C57BL/6 mice and fails to do so in strain- and sex-matched adults. Furthermore, we find that the age-dependent effect of isoproterenol on spike frequency is occluded by the GABAA receptor blocker picrotoxin (75 µM), suggesting that ß-adrenergic receptors downregulate tonic inhibition specifically in juvenile animals. These findings indicate a significant shift during adolescence in the cellular mechanisms of ß-adrenergic modulation in the amygdala. NEW & NOTEWORTHY ß-Adrenergic receptors (ß-ARs) in amygdala are important in processing emotionally salient stimuli. Most cellular recordings have examined juvenile animals, while behavioral data are often obtained from adults. We replicate findings showing that ß-ARs enhance spiking of principal cells in the lateral amygdala of juveniles, but we fail to find this in adults. These findings have notable scientific and clinical implications regarding the noradrenergic modulation of threat processing, alterations of which underlie fear and anxiety disorders.
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Agonistas Adrenérgicos beta/farmacología , Complejo Nuclear Basolateral/fisiología , Fenómenos Electrofisiológicos/fisiología , Antagonistas de Receptores de GABA-A/farmacología , Receptores Adrenérgicos beta/fisiología , Factores de Edad , Animales , Complejo Nuclear Basolateral/efectos de los fármacos , Fenómenos Electrofisiológicos/efectos de los fármacos , Isoproterenol/farmacología , Masculino , Ratones Endogámicos C57BL , Técnicas de Placa-Clamp , Picrotoxina/farmacología , Receptores Adrenérgicos beta/efectos de los fármacosRESUMEN
Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used muscimol infusions in rats to show that discriminatory threat learning requires Au1 activity specifically during memory acquisition and retrieval, but not during consolidation. Memory specificity was similarly disrupted by infusion of PKMζ inhibitor peptide (ZIP) during memory storage. Our findings show that Au1 is required at critical memory phases and suggest that Au1 plasticity enables stimulus discrimination.
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Corteza Auditiva/fisiología , Condicionamiento Clásico/fisiología , Miedo/fisiología , Memoria/fisiología , Análisis de Varianza , Animales , Corteza Auditiva/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Discriminación en Psicología/efectos de los fármacos , Discriminación en Psicología/fisiología , Inhibidores Enzimáticos/farmacología , Miedo/efectos de los fármacos , Agonistas de Receptores de GABA-A/farmacología , Memoria/efectos de los fármacos , Muscimol/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , RatasRESUMEN
The creation of auditory threat Pavlovian memory requires an initial learning stage in which a neutral conditioned stimulus (CS), such as a tone, is paired with an aversive one (US), such as a shock. In this phase, the CS acquires the capacity of predicting the occurrence of the US and therefore elicits conditioned defense responses. Norepinephrine (NE), through ß-adrenergic receptors in the amygdala, enhances threat memory by facilitating the acquisition of the CS-US association, but the nature of this effect has not been described. Here we show that NE release, induced by the footshock of the first conditioning trial, promotes the subsequent enhancement of learning. Consequently, blocking NE transmission disrupts multitrial but not one-trial conditioning. We further found that increasing the time between the conditioning trials eliminates the amplificatory effect of NE. Similarly, an unsignaled footshock delivered in a separate context immediately before conditioning can enhance learning. These results help define the conditions under which NE should and should not be expected to alter threat processing and fill an important gap in the understanding of the neural processes relevant to the pathophysiology of stress and anxiety disorders.
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Amígdala del Cerebelo/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Miedo/efectos de los fármacos , Memoria a Largo Plazo/efectos de los fármacos , Norepinefrina/farmacología , Antagonistas Adrenérgicos beta/farmacología , Amígdala del Cerebelo/fisiología , Análisis de Varianza , Animales , Condicionamiento Clásico/fisiología , Electrochoque/efectos adversos , Extinción Psicológica/efectos de los fármacos , Reacción Cataléptica de Congelación/efectos de los fármacos , Reacción Cataléptica de Congelación/fisiología , Masculino , Propranolol/farmacología , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
The updating of a memory is triggered whenever it is reactivated and a mismatch from what is expected (i.e., prediction error) is detected, a process that can be unraveled through the memory's sensitivity to protein synthesis inhibitors (i.e., reconsolidation). As noted in previous studies, in Pavlovian threat/aversive conditioning in adult rats, prediction error detection and its associated protein synthesis-dependent reconsolidation can be triggered by reactivating the memory with the conditioned stimulus (CS), but without the unconditioned stimulus (US), or by presenting a CS-US pairing with a different CS-US interval than during the initial learning. Whether similar mechanisms underlie memory updating in the young is not known. Using similar paradigms with rapamycin (an mTORC1 inhibitor), we show that preweaning rats (PN18-20) do form a long-term memory of the CS-US interval, and detect a 10-sec versus 30-sec temporal prediction error. However, the resulting updating/reconsolidation processes become adult-like after adolescence (PN30-40). Our results thus show that while temporal prediction error detection exists in preweaning rats, specific infant-type mechanisms are at play for associative learning and memory.
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Envejecimiento/fisiología , Reacción de Prevención/fisiología , Condicionamiento Clásico/fisiología , Memoria/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Envejecimiento/efectos de los fármacos , Animales , Animales Recién Nacidos , Reacción de Prevención/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Señales (Psicología) , Relación Dosis-Respuesta a Droga , Extinción Psicológica/efectos de los fármacos , Extinción Psicológica/fisiología , Miedo/efectos de los fármacos , Femenino , Reacción Cataléptica de Congelación/efectos de los fármacos , Reacción Cataléptica de Congelación/fisiología , Inmunosupresores/farmacología , Masculino , Memoria/efectos de los fármacos , Ratas , Ratas Long-Evans , Ratas Sprague-Dawley , Sirolimus/farmacología , Gusto/efectos de los fármacos , Gusto/fisiologíaRESUMEN
Fear arousal, initiated by an environmental threat, leads to activation of the stress response, a state of alarm that promotes an array of autonomic and endocrine changes designed to aid self-preservation. The stress response includes the release of glucocorticoids from the adrenal cortex and catecholamines from the adrenal medulla and sympathetic nerves. These stress hormones, in turn, provide feedback to the brain and influence neural structures that control emotion and cognition. To illustrate this influence, we focus on how it impacts fear conditioning, a behavioral paradigm widely used to study the neural mechanisms underlying the acquisition, expression, consolidation, reconsolidation, and extinction of emotional memories. We also discuss how stress and the endocrine mediators of the stress response influence the morphological and electrophysiological properties of neurons in brain areas that are crucial for fear-conditioning processes, including the amygdala, hippocampus, and prefrontal cortex. The information in this review illuminates the behavioral and cellular events that underlie the feedforward and feedback networks that mediate states of fear and stress and their interaction in the brain.