Predator fear memory depends on glucocorticoid receptors and protein synthesis in the basolateral amygdala and ventral hippocampus.

Previous studies have suggested that the basolateral amygdala (BLA) and the ventral hippocampus (VH) are critical sites for predator-related fear memory. Predator exposure is an intense emotional experience and should increase plasmatic corticosterone likely to modulate the emotion-related memories. However, it is unclear whether the BLA and VH harbor plastic events underlying predator-related fear memory storage and how molecular and endocrine mechanisms interact to modulate memory to the predatory threat. Here, we first examined the effects of protein synthesis inhibition in the BLA and VH on fear memory to a predatory threat. We next evaluated how exposure to a predatory threat impacts the corticosterone release and how the inhibition of corticosterone synthesis can influence predator-related fear memory. Finally, we examined how predator exposure triggers the activation of glucocorticoid and mineralocorticoid receptors in the BLA and VH and whether the GR antagonist injection affects predator-related fear memory. We showed that predator-related contextual fear is dependent on protein synthesis in the BLA and VH. Moreover, we described the impact of rapid glucocorticoid release during predatory exposure on the formation of contextual fear responses and that GR-induced signaling facilitates memory consolidation within the BLA and VH. The results are relevant in understanding how life-threatening situations such as a predator encounter impact fear memory storage and open exciting perspectives to investigate GR-induced proteins as targets to deciphering and manipulating aversive memories.

Neural correlates of distinct levels of predatory threat in dorsal periaqueductal grey neurons.

The dorsal periaqueductal grey (PAG) is an important site for integrating predatory threats. However, it remains unclear whether predator-related activation in PAG primarily reflects threat itself and thus can distinguish between various degrees of threat, or rather reflects threat-oriented behaviours, with the PAG potentially orchestrating different types of defensive repertoire. To address this issue, we performed extracellular recording of dorsal PAG neurons in freely behaving rats and examined neuronal and behavioural responses to stimulus conditions with distinct levels of predatory threat. Animals were sequentially exposed to a nonthreatening stimulus familiar environment (exposure to habituated environment) and to a novel nonthreatening stimulus (i.e., a toy animal-plush) and to conditions with high (exposure to a live cat), intermediate (exposure to the environment just visited by the cat, with remnant predator scent), and low (exposure on the following day to the predatory context) levels of predatory threat. To test for contributions of both threat stimuli and behaviour to changes in firing rate, we applied a Poisson generalized linear model regression, using the different predator stimulus conditions and defensive repertoires as predictor variables. Analysis revealed that the different predator stimulus conditions were more predictive of changes in firing rate (primarily threat-induced increases) than the different defensive repertoires. Thus, the dorsal PAG may code for different levels of predatory threat, more than it directly orchestrates distinct threat-oriented behaviours. The present results open interesting perspectives to investigate the role of the dorsal PAG in mediating primal emotional and cognitive responses to fear-inducing stimuli.

The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats.

Predator exposure is a life-threatening experience and elicits learned fear responses to the context in which the predator was encountered. The anterior cingulate area (ACA) occupies a pivotal position in a cortical network responsive to predatory threats, and it exerts a critical role in processing fear memory. The experiments were made in mice and revealed that the ACA is involved in both the acquisition and expression of contextual fear to predatory threat. Overall, the ACA can provide predictive relationships between the context and the predator threat and influences fear memory acquisition through projections to the basolateral amygdala and perirhinal region and the expression of contextual fear through projections to the dorsolateral periaqueductal gray. Our results expand previous studies based on classical fear conditioning and open interesting perspectives for understanding how the ACA is involved in processing contextual fear memory to ethologic threatening conditions that entrain specific medial hypothalamic fear circuits.

Defensive behaviors and brain regional activation changes in rats confronting a snake.

In the present study, we examined behavioral and brain regional activation changes of rats). To a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

The rostrodorsal periaqueductal gray influences both innate fear responses and acquisition of fear memory in animals exposed to a live predator.

A few studies have evaluated the behavioral roles of the periaqueductal gray (PAG) in animals facing ethologically relevant threats. Exposure to a live cat induces striking activation in the rostrodorsal and caudal ventral PAG. In the present investigation, we first showed that cytotoxic lesions of the rostrodorsal and caudal ventral PAG had similar effects on innate fear responses during cat exposure, practically abolishing freezing and increasing risk assessment responses. Conversely, rostrodorsal PAG lesions but not caudal ventral lesions disrupted learned contextual fear responses to cat exposure. Next, we examined how muscimol inactivation of the rostrodorsal PAG at different times (i.e., during, immediately after and 20 min after cat exposure) influences learned contextual fear responses, and we found that inactivation of the rostrodorsal PAG during or immediately after cat exposure but not 20 min later impaired contextual fear learning. Thus, suggesting that the rostrodorsal PAG is involved in the acquisition, but not the consolidation, of contextual fear memory to predatory threat. Notably, the dosolateral PAG contains a distinct population of neurons containing the neuronal nitric oxide synthase (nNOS) enzyme, and in the last experiment, we investigated how nitric oxide released in rostrodorsal PAG influences contextual fear memory processing. Accordingly, injection of a selective nNOS inhibitor into the rostrodorsal PAG immediately after cat exposure disrupted learned contextual responses. Overall, the present findings suggest that the acquisition of contextual fear learning is influenced by an optimum level of dorsal PAG activation, which extends from during to shortly after predator exposure and depends on local NO release.

Revealing a Cortical Circuit Responsive to Predatory Threats and Mediating Contextual Fear Memory.

The ventral part of the anteromedial thalamic nucleus (AMv) receives substantial inputs from hypothalamic sites that are highly responsive to a live predator or its odor trace and represents an important thalamic hub for conveying predatory threat information to the cerebral cortex. In the present study, we begin by examining the cortico-amygdalar-hippocampal projections of the main AMv cortical targets, namely, the caudal prelimbic, rostral anterior cingulate, and medial visual areas, as well as the rostral part of the ventral retrosplenial area, one of the main targets of the anterior cingulate area. We observed that these areas form a clear cortical network. Next, we revealed that in animals exposed to a live cat, all of the elements of this circuit presented a differential increase in Fos, supporting the idea of a predator threat-responsive cortical network. Finally, we showed that bilateral cytotoxic lesions in each element of this cortical network did not change innate fear responses but drastically reduced contextual conditioning to the predator-associated environment. Overall, the present findings suggest that predator threat has an extensive representation in the cerebral cortex and revealed a cortical network that is responsive to predatory threats and exerts a critical role in processing fear memory.

Roles of the anterior basolateral amygdalar nucleus during exposure to a live predator and to a predator-associated context.

The basolateral amygdala complex, which includes the lateral, basolateral and basomedial nuclei, has been implicated in innate and contextual fear responses to predator threats. In the basolateral complex, the lateral and posterior basomedial nuclei are able to process predator odor information, and they project to the predator-responsive hypothalamic circuit; lesions in these amygdalar sites reduce innate responses and practically abolish contextual fear responses to predatory threats. In contrast to the lateral and posterior basomedial nuclei, the basolateral nucleus does not receive direct information from predator olfactory cues and has no direct link to the predator-responsive hypothalamic circuit. No attempt has previously been made to determine the specific role of the basolateral nucleus in fear responses to predatory threats, and we currently addressed this question by making bilateral N-methyl-D-aspartate lesions in the anterior basolateral nucleus of the amygdala (BLAa), which is often regarded as being contiguous with the lateral amygdalar nucleus, and tested both innate and contextual fear in response to cat exposure. Accordingly, BLAa lesions decreased both innate and contextual fear responses to predator exposure. Considering the targets of the BLAa, the nucleus accumbens appears to be a potential candidate to influence innate defensive responses to predator threats. The present findings also suggest that the BLAa has a role in fear memory of predator threat. The BLAa is likely involved in memory consolidation, which could potentially engage BLAa projection targets, opening interesting possibilities in the investigation of how these targets could be involved in the consolidation of predator-related fear memory.

Influence of the anteromedial thalamus on social defeat-associated contextual fear memory.

The ventral part of the anteromedial thalamic nucleus (AMv) is heavily targeted by the dorsal premammillary nucleus (PMd), which is the main hypothalamic site that is responsive to both predator and conspecific aggressor threats. This PMd-AMv pathway is likely involved in modulating memory processing, and previous findings from our group have shown that cytotoxic lesions or pharmacological inactivation of the AMv drastically reduced contextual fear responses to predator-associated environments. In the present study, we investigated the role of the AMv in both unconditioned (i.e., fear responses during social defeat) and contextual fear responses (i.e., during exposure to a social defeat-associated context). We addressed this question by placing N-methyl-d-aspartate (NMDA) lesions in the AMv and testing unconditioned fear responses during social defeat and contextual fear responses during exposure to a social defeat-associated context. Accordingly, bilateral AMv lesions did not change unconditioned responses, but decreased contextual conditioning related to social defeat. Notably, our bilateral AMv lesions also included, to a certain degree, the nucleus reuniens (RE), but single RE lesions did not affect innate or contextual fear responses. Overall, our results support the idea that the AMv works as a critical hub, receiving massive inputs from a hypothalamic site that is largely responsive to social threats and transferring social threat information to circuits involved in the processing of contextual fear memories.

A role for the anteromedial thalamic nucleus in the acquisition of contextual fear memory to predatory threats.

Previous studies from our group have shown that cytotoxic lesions in the ventral portion of the anteromedial thalamic nucleus (AMv), one of the main targets of the hypothalamic predator-responsive circuit, strongly impairs contextual fear responses to an environment previously associated with a predator. The AMv is in a position to convey information to cortico-hippocampal-amygdalar circuits involved in the processing of fear memory. However, it remains to be determined whether the nucleus is involved in the acquisition or subsequent expression of contextual fear. In the present investigation, we addressed this question by inactivating the rat AMv with muscimol either prior to cat exposure or prior to exposure to the cat-related context. Accordingly, AMv pharmacological inactivation prior to cat exposure did not interfere with innate fear responses, but it drastically reduced contextual conditioning to the predator-associated environment. On the other hand, AMv inactivation prior to exposure to the environment associated with the predator threat did not affect contextual fear responses. The behavioral results were further supported by the demonstration that AMv inactivation prior to cat exposure also blocked the activation of sites critically involved in the expression of anti-predatory contextual defensive responses (i.e., the dorsal premammillary nucleus and the dorsolateral periaqueductal gray) in animals exposed to the predator-associated context. The AMv projections were also examined, and the results of this investigation outline important paths that can influence hippocampal circuitry and raise new ideas for anterior thalamic-hippocampal paths involved in emotional learning.

Testing conditions in shock-based contextual fear conditioning influence both the behavioral responses and the activation of circuits potentially involved in contextual avoidance.

Previous studies from our group have shown that risk assessment behaviors are the primary contextual fear responses to predatory and social threats, whereas freezing is the main contextual fear response to physically harmful events. To test contextual fear responses to a predator or aggressive conspecific threat, we developed a model that involves placing the animal in an apparatus where it can avoid the threat-associated environment. Conversely, in studies that use shock-based fear conditioning, the animals are usually confined inside the conditioning chamber during the contextual fear test. In the present study, we tested shock-based contextual fear responses using two different behavioral testing conditions: confining the animal in the conditioning chamber or placing the animal in an apparatus with free access to the conditioning compartment. Our results showed that during the contextual fear test, the animals confined to the shock chamber exhibited significantly more freezing. In contrast, the animals that could avoid the conditioning compartment displayed almost no freezing and exhibited risk assessment responses (i.e., crouch-sniff and stretch postures) and burying behavior. In addition, the animals that were able to avoid the shock chamber had increased Fos expression in the juxtadorsomedial lateral hypothalamic area, the dorsomedial part of the dorsal premammillary nucleus and the lateral and dorsomedial parts of the periaqueductal gray, which are elements of a septo/hippocampal-hypothalamic-brainstem circuit that is putatively involved in mediating contextual avoidance. Overall, the present findings show that testing conditions significantly influence both behavioral responses and the activation of circuits involved in contextual avoidance.

Modulation of perceived contrast in the brightness comparison of asynchronous stimuli.

Comparative judgment is a crucial task in ecological settings, as well as in many experimental studies about basic aspects of perceptual processes. It has long been known that sequential comparison is prone to order effects. This phenomenon has received little attention and has often been discounted as a type of response bias. In the present study, we investigated brightness discrimination of two brief (100 ms) spatially disjoint luminance stimuli. In the first and second experiments, stimuli were presented against a dark background with a stimulus onset asynchrony (SOA) from 0 to 200 ms, in a paradigm controlling for response bias. In the third experiment, stimuli were presented against a bright background. We demonstrate that the time interval between stimuli modulates and even inverts their perceived brightness difference, enhancing the second stimulus relative to the first. When the background is brighter than the target stimuli, the sign of the effect is inverted, suggesting that the underlying mechanism operates on contrast rather than brightness. The magnitude of this effect is shown to depend on SOA and average luminance level of the target stimuli. Hypotheses in terms of neural and attentional dynamics are proposed.

Signal detection theory in Hilbert space.

The Hilbert space formalism is a powerful language to express many cognitive phenomena. Here, relevant concepts from signal detection theory are recast in that language, allowing an empirically testable extension of the quantum probability formalism to psychophysical measures, such as detectability and discriminability.

Evidence for the thalamic targets of the medial hypothalamic defensive system mediating emotional memory to predatory threats.

Previous studies from our laboratory have documented that the medial hypothalamic defensive system is critically involved in processing actual and contextual predatory threats, and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats. Anatomical findings suggest that the PMd is in a position to modulate memory processing through a projecting branch to specific thalamic nuclei, i.e., the nucleus reuniens (RE) and the ventral part of the anteromedial nucleus (AMv). In the present study, we investigated the role of these thalamic targets in both unconditioned (i.e., fear responses to predatory threat) and conditioned (i.e., contextual responses to predator-related cues) defensive behaviors. During cat exposure, all experimental groups exhibited intense defensive responses with the animals spending most of the time in the home cage displaying freezing behavior. However, during exposure to the environment previously associated with a cat, the animals with combined RE+AMv lesions, and to a lesser degree, animals with single AMv unilateral lesions, but not animals with single RE lesions, presented a reduction of contextual conditioned defensive responses. Overall, the present results provide clear evidence suggesting that the PMd's main thalamic targets (i.e., the nucleus reuniens and the AMv) seem to be critically involved in the emotional memory processing related to predator cues.

The time of perception and the other way around.

The world we perceive is delayed in relation to its flowing content, as well as the outcome of our actions on the world in relation to the moment we decide to act. This mosaic of different latencies permeating both perception and action has to be taken into account critically in order for us to cope with the temporal challenges constantly imposed by the environment. Fundamental notions, such as the sense of agency and causality, depend on the temporal relationship of events occurring in well-defined windows of time. Here, we offer a broad, yet abridged, historical view of some thought-provoking issues concerning the time of perception and action. From the pioneering work of Wundt, Titchener, and Libet to recent findings and ideas related to the employment of visual illusions as psychophysical probes (such as the flash-lag effect), we have tried to expose some problems inherent to the act of measuring the time of both perception and action, and devise possible solutions as well.

The time of perception and the other way around

The world we perceive is delayed in relation to its flowing content, as well as the outcome of our actions on the world in relation to the moment we decide to act. This mosaic of different latencies permeating both perception and action has to be taken into account critically in order for us to cope with the temporal challenges constantly imposed by the environment. Fundamental notions, such as the sense of agency and causality, depend on the temporal relationship of events occurring in well-defined windows of time. Here, we offer a broad, yet abridged, historical view of some thought-provoking issues concerning the time of perception and action. From the pioneering work of Wundt, Titchener, and Libet to recent findings and ideas related to the employment of visual illusions as psychophysical probes (such as the flash-lag effect), we have tried to expose some problems inherent to the act of measuring the time of both perception and action, and devise possible solutions as well (AU)

El mundo que percibimos está retardado en relación a su flujo de contenido, al igual que el resultado de nuestras acciones sobre el mundo en relación con el momento en que decidamos actuar. Este mosaico de diferentes latencias que penetra tanto en la percepción como en la acción debe ser tenido en cuenta de forma crítica para poder manejar los retos temporales constantemente impuestos por el entorno. Nociones fundamentales, como el sentido de ser un agente y el de la causalidad, dependen de la relación temporal de los eventos que ocurren en ventanas bien definidas de tiempo. Aquí ofrecemos un panorama histórico extenso pero abreviado de algunas cuestiones provocadoras de la reflexión acerca del tiempo de la percepción y de la acción. Desde los trabajos pioneros de Wundt, Titchener y Libet hasta los descubrimientos recientes y las ideas relacionadas con el empleo de las ilusiones ópticas tales como el efecto «flash-lag», como sondas psicofísicas, hemos intentado exponer algunos de los problemas inherentes al acto de medir el tiempo, tanto el de la percepción como el de la acción, así como diseñar soluciones posibles (AU)

Ilusöes: o olho mágico da percepçäo / Illusions: a window into perception

A percepçäo é a construçäo ativa de um estado neural que se correlaciona a elementos biologicamente relevantes do ambiente. Esta correlaçäo, longe de estabelecer uma representaçäo fiel do mundo, guia nossas açöes na elaboraçäo de comportamentos adaptativos, sendo, portanto, condicionada por fatores evolutivos. Já que a construçäo de um percepto é um processo intrinsecamente ambíguo, discrepâncias perceptivas podem surgir a partir de condiçöes idênticas de estimulaçäo. Essas discrepâncias säo denominadas ilusöes, e se originam dos mesmos mecanismos fisiológicos que produzem a nossa percepçäo cotidiana. Derivando de diferentes fatores, tais como ópticos, sensoriais e cognitivos, as ilusöes visuais säo instrumentos úteis na exploraçäo das bases fisiológicas da percepçäo e de sua interaçäo com o planejamento e execuçäo de açöes motoras. Aqui, examinamos as origens biológicas das ilusöes visuais e algumas de suas relaçöes com aspectos neurobiológicos, filosóficos e estéticos

[Illusions: a window into perception]. / Ilusões: o olho mágico da percepção.

Perception is the active construction of a neural state that correlates with biologically relevant elements present in the environment. This correlation, far from affording a one-to-one mapping, nonetheless guides our actions towards adaptive behaviors, thus being forged under evolutionary constraints. Since the construction of a percept is an intrinsically ambiguous process, perceptual discrepancies can arise from identical stimulation patterns. The recognition of these discrepancies is termed illusion, which originates, however, from the same physiological mechanisms that ordinarily lead to standard perception. Emanating from different sources, such as optical, sensory and cognitive factors, visual illusions are useful tools in accessing the physiological basis of perceptual processes and their interaction with motor planning and execution. Here we examine the biological roots of visual illusions and their interplay with some neurobiological, philosophical and esthetical issues.

Flag errors in soccer games: the flash-lag effect brought to real life.

In soccer games, an attacking player is said to be in an offside position if he or she is closer to the opponents' goal line than both the ball and the second-to-last defender. It is an offence for the attacker to be in an offside position and in active play at the moment a fellow team member plays the ball. Assistant referees often make mistakes when judging an offside offence, probably because of optical errors arising from the viewing angle adopted by them (Oudejans, Verheijen, Bakker, Gerrits, Steinbrückner, Beek, 2000 Nature 404 33). Looking more closely at Oudejans et al's data, we show evidence that the flash-lag effect may contribute significantly to these mistakes. Participation of the flash-lag effect in assistant referees' misjudgments would take this perceptual phenomenon from laboratory setups to a real-life situation for the first time.