Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice / 神经科学通报·英文版

Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.

Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice / 神经科学通报·英文版

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca2+ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca2+ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca2+ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.

Advances in neural circuits of innate fear defense behavior / 浙江大学学报·医学版

Fear, a negative emotion triggered by dangerous stimuli, can lead to psychiatric disorders such as phobias, anxiety disorders, and depression. Investigating the neural circuitry underlying congenital fear can offer insights into the pathophysiological mechanisms of related psychiatric conditions. Research on innate fear primarily centers on the response mechanisms to various sensory signals, including olfactory, visual and auditory stimuli. Different types of fear signal inputs are regulated by distinct neural circuits. The neural circuits of the main and accessory olfactory systems receive and process olfactory stimuli, mediating defensive responses like freezing. Escape behaviors elicited by visual stimuli are primarily regulated through the superior colliculus and hypothalamic projection circuits. Auditory stimuli-induced responses, including escape, are mainly mediated through auditory cortex projection circuits. In this article, we review the research progress on neural circuits of innate fear defensive behaviors in animals. We further discuss the different sensory systems, especially the projection circuits of olfactory, visual and auditory systems, to provide references for the mechanistic study of related mental disorders.

Formation of the Looming-evoked Innate Defensive Response during Postnatal Development in Mice / 神经科学通报·英文版

Environmental threats often trigger innate defensive responses in mammals. However, the gradual development of functional properties of these responses during the postnatal development stage remains unclear. Here, we report that looming stimulation in mice evoked flight behavior commencing at P14-16 and had fully developed by P20-24. The visual-evoked innate defensive response was not significantly altered by sensory deprivation at an early postnatal stage. Furthermore, the percentages of wide-field and horizontal cells in the superior colliculus were notably elevated at P20-24. Our findings define a developmental time window for the formation of the visual innate defense response during the early postnatal period and provide important insight into the underlying mechanism.

Medo de quedas e força muscular do quadril em idosos independentes da comunidade / Miedo a caerse y fuerza muscular de cadera en ancianos independientes de la comunidad / Fear of falling and hip muscular strength in independent older adults of the community

RESUMO O medo de quedas pode fazer com que o idoso desenvolva estratégias que alteram o equilíbrio semiestático e dinâmico, predispondo-o a um risco aumentado de cair. A função muscular dos abdutores e adutores de quadril tem importante papel na manutenção da estabilidade postural. Entretanto, não se sabe se idosos com medo de cair apresentam maior comprometimento na função muscular do quadril. Assim, o objetivo foi comparar o pico de torque (PT) isométrico dos músculos abdutores e adutores de quadril entre idosos com e sem medo de quedas. Os participantes foram divididos em dois grupos: com (n=81) e sem (n=81) medo de quedas. O PT dos abdutores e adutores de quadril foi obtido com dinamômetro isocinético (System 4 Pro, Biodex, Nova York, EUA). A comparação do PT dos grupos foi realizada por meio de modelo linear geral univariado, ajustado pelas covariáveis idade, sexo, índice de massa corporal, nível de atividade física e histórico de quedas, utilizando o software SPSS 17.0, com nível de significância de 5%. Não houve diferença do PT abdutor e adutor do quadril entre os grupos após análise univariada com ajustamento. Observou-se que idosos com medo de quedas não apresentam prejuízos na função muscular dos estabilizadores de quadril quando comparados a idosos sem medo de quedas.

RESUMEN El miedo a caerse puede hacer que los ancianos desarrollen estrategias de alteración del equilibrio semiestático y dinámico, predisponiéndolos a un mayor riesgo de caídas. La función muscular de los abductores y de los aductores de cadera juega un papel importante en el mantenimiento de la estabilidad postural. Sin embargo, no se sabe si los ancianos con miedo a caerse tienen un mayor deterioro en la función muscular de la cadera. Por lo tanto, el objetivo fue comparar el torque máximo (TM) isométrico de los músculos abductores y aductores de cadera entre los ancianos con miedo y sin miedo a caerse. Los participantes se dividieron en dos grupos: con miedo a caerse (n=81) y sin (n=81) miedo a caerse. El TM de los abductores y aductores de cadera se obtuvo mediante la utilización del dinamómetro isocinético (System 4 Pro, Biodex, Nueva York, EE.UU.). La comparación del TM de los grupos se realizó mediante un modelo lineal general univariado, ajustado por covariables edad, género, índice de masa corporal, nivel de actividad física e historial de caídas, utilizando el software SPSS 17.0, con nivel de significancia del 5%. No hubo diferencias entre el TM del abductor y del aductor de cadera entre los grupos tras el análisis univariado con ajuste. Se observó que los ancianos con miedo a caerse no presentaron daños en la función muscular de los estabilizadores de la cadera en comparación con los ancianos sin miedo a caerse.

ABSTRACT The fear of falling can cause older adults to develop strategies that alter the semi-static and dynamic balance, predisposing them to increased risk of falling. The muscular function of abductors and adductors plays an important role in maintaining postural stability. However, it is unknown whether older people with fear of falling have greater impairment in hip muscular function. Thus, the objective was to compare the isometric peak torque (PT) of hip abductor and adductor muscles among older adults with and without fear of falling. Participants were divided into two groups: with (n=81) and without (n=81) fear of falling. The PT of hip abductors and adductors was obtained with isokinetic dynamometer (System 4 Pro, Biodex, New York, USA). The PT groups were compared using general linear model univariate, adjusted for covariates age, sex, body mass index, physical activity level and history of falls, using the SPSS 17.0 software, with a significance level of 5%. No difference was found between the PT of hip abductor and adductor and the groups after univariate analysis with adjustment. We observed that older people with fear of falling have no muscle function loss of the hip stabilizers when compared with subjects without fear of falling.

The elevated gradient of aversion: a new apparatus to study the rat behavior dimensions of anxiety, fear, and impulsivity

Few behavioral tests allow measuring several characteristics and most require training, complex analyses, and/or are time-consuming. We present an apparatus based on rat exploratory behavior. Composed of three different environments, it allows the assessment of more than one behavioral characteristic in a short 3-min session. Factorial analyses have defined three behavioral dimensions, which we named Exploration, Impulsivity, and Self-protection. Behaviors composing the Exploration factor were increased by chlordiazepoxide and apomorphine and decreased by pentylenetetrazole. Behaviors composing the Impulsivity factor were increased by chlordiazepoxide, apomorphine, and both acute and chronic imipramine treatments. Behaviors composing the Self-protection factor were decreased by apomorphine. We submitted Wistar rats to the open-field test, the elevated-plus maze, and to the apparatus we are proposing. Measures related to exploratory behavior in all three tests were correlated. Measures composing the factors Impulsivity and Self-protection did not correlate with any measures from the two standard tests. Also, compared with existing impulsivity tests, the one we proposed did not require previous learning, training, or sophisticated analysis. Exploration measures from our test are as easy to obtain as the ones from other standard tests. Thus, we have proposed an apparatus that measured three different behavioral characteristics, was simple and fast, did not require subjects to be submitted to previous learning or training, was sensitive to drug treatments, and did not require sophisticated data analyses.

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

Objective: To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. Methods: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors’ research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined. Results: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. Conclusions: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.

The joint structure of major depression, anxiety disorders, and trait negative affect

Background: Dimensional models of psychopathology demonstrate that two correlated factors of fear and distress account for the covariation among depressive and anxiety disorders. Nevertheless, these models tend to exclude variables relevant to psychopathology, such as temperament traits. This study examined the joint structure of DSM-IV-based major depression and anxiety disorders along with trait negative affect in a representative sample of adult individuals residing in the cities of São Paulo and Rio de Janeiro, Brazil. Methods: The sample consisted of 3,728 individuals who were administered sections D (phobic, anxiety and panic disorders) and E (depressive disorders) of the Composite International Diagnostic Interview (CIDI) 2.1 and a validated version of the Positive and Negative Affect Schedule. Data were analyzed using correlational and structural equation modeling. Results: Lifetime prevalence ranged from 2.4% for panic disorder to 23.2% for major depression. Most target variables were moderately correlated. A two-factor model specifying correlated fear and distress factors was retained and confirmed for models including only diagnostic variables and diagnostic variables along with trait negative affect. Conclusions: This study provides support for characterization of internalizing psychopathology and trait negative affect in terms of correlated dimensions of distress and fear. These results have potential implications for psychiatric taxonomy and for understanding the relationship between temperament and psychopathology. .

Hipnosis como complemento en la cirugía oral del adulto mayor / Hypnosis as a complement to oral surgery in elderly persons

Introducción: el envejecimiento poblacional es un fenómeno mundial y la cirugía oral es compleja en los adultos mayores, por lo que la preparación preoperatoria es de vital importancia para una evolución satisfactoria. Este trabajo tiene como objetivo demostrar la eficacia de la hipnosis en pacientes con temor en la cirugía oral del adulto mayor. Métodos: se realizó un estudio descriptivo, transversal, con muestra de 20 pacientes de 60 años o más, atendidos en la consulta de Cirugía Maxilofacial del Hospital Universitario Comandante Manuel Fajardo, en el año 2011, donde se analizaron las variables edad, sexo, número de sesiones de hipnosis, antecedentes patológicos, diagnósticos más frecuentes y temor. Resultados: el mayor número de pacientes se encontró entre 60-69 años de edad, (70 por ciento) y el menor en 70-79, (30 por ciento). El sexo femenino prevaleció con 70 por ciento. El número de sesiones fue en el grupo de 60-69 con 58, con un promedio total de 4 por pacientes. En los antecedentes patológicos más frecuentes fue la hipertensión arterial en 14 (70 por ciento) y le siguió la diabetes tipo II en 2 (10 por ciento). En los diagnósticos más frecuentes fue la caries de cuarto grado con 10 (50 por ciento) seguido por los dientes parodontósicos con 4 (20 por ciento). El temor se midió en una escala confeccionada, en la que los pacientes con cifras de l0, 8 y 7 se redujeron a 4 y 5. Conclusiones: Se demuestra la efectividad de la terapia de hipnosis para disminuir el temor y realizar la cirugía oral en el adulto mayor(AU)

Introduction: population aging is a worldwide phenomenon, and oral surgery is complex in elderly patients. Therefore, preoperative preparation is vital to their satisfactory evolution. The purpose of the present paper is to show the efficacy of hypnosis in elderly patients who fear oral surgery. Methods: a descriptive cross-sectional study was conducted with a sample of 20 patients aged 60 or over, cared for at the maxillofacial surgery service of Comandante Manuel Fajardo University Hospital in the year 2011. The variables analyzed were age, sex, number of hypnotic sessions, disease history, most frequent diagnoses and fear. Results: most patients fell into the 60-69 age group (70 percent). The remaining 30 percent were in the 70-79 age group. Female sex predominated with 70 percent. The highest number of sessions was 58 in the 60-69 age group, with an average of 4 per patient. The most frequent pathological antecedents were hypertension in 14 (70 percent), followed by type II diabetes in 2 (10 percent). The most common diagnoses were fourth degree caries in 10 (50 percent), followed by parodontic teeth in 4 (20 percent). Fear was measured with a dedicated scale on which patient scores of 10, 8 and 7 were reduced to 4 and 5. Conclusions: hypnotic therapy was shown to be effective to relieve fear of oral surgery in elderly persons(AU)

Spectral characteristics of the hippocampal LFP during contextual fear conditioning / Características espectrais da atividade elétrica hipocampal durante o medo condicionado ao contexto

Objective: The hippocampus has an important role in the acquisition and recall of aversive memories. The objective of this study was to investigate the relationship among hippocampal rhythms. Methods: Microeletrodes arrays were implanted in the hippocampus of Wistar rats. The animals were trained and tested in a contextual fear conditioning task. The training consisted in applying shocks in the legs. The memory test was performed 1 day (recent memory) or 18 days (remote memory) after training. We proposed a measure based on the FFT power spectrum, denominated "delta-theta ratio", to characterize the different behaviors (active exploration and freezing) and the memories types. Results: The delta-theta ratio was able to distinguish recent and remote memories. In this study, the ratio for the 18-day group was smaller than for the 1-day group. Moreover, this measure was useful to distinguish the different behavior states - active exploration and freezing. Conclusions: The results suggest delta-theta oscillations could reflect the demands on information processing during recent and remote memory recalls.

Objetivo: O hipocampo tem um importante papel na aquisição e evocação das memórias aversivas. Pretendeu-se, neste trabalho, investigar a dinâmica entre os ritmos hipocampais durante a evocação das memórias aversivas recente e remota. Métodos: Foram implantadas matrizes de microeletrodos em ratos Wistar. Os animais foram treinados e testados numa tarefa de condicionamento contextual de medo. O treino consistiu em aplicações de choques nas patas. O teste de memória foi realizado 1 dia (memória recente) ou 18 dias (memória remota) após o treino. Nesse trabalho, foi proposta uma medida baseada no espectro de potências, denominada "razão delta-theta", para caracterização dos diferentes comportamentos observados (vigília exploratória e congelamento) e tipos de memórias. Resultados: A razão delta-theta mostrou-se capaz de distinguir os grupos testados para as memórias recente e remota. Neste caso, observou-se, para o grupo testado 18 dias após, um valor menor do que para o grupo testado 1 dia após. Além disso, essa medida mostrou-se útil para distinguir os diferentes estados comportamentais. Conclusões: Os resultados sugerem que a dinâmica entre os ritmos delta e theta pode refletir o processamento da informação durante a evocação das memórias recente e remota.

Outlining new frontiers for the comprehension of obsessive-compulsive disorder: a review of its relationship with fear and anxiety / Desenhando as novas fronteiras para a compreensão do transtorno obsessivo-compulsivo: uma revisão de sua relação com o medo e a ansiedade

Anxiety is an important component of the psychopathology of the obsessive-compulsive disorder (OCD). So far, most interventions that have proven to be effective for treating OCD are similar to those developed for other anxiety disorders. However, neurobiological studies of OCD came to conclusions that are not always compatible with those previously associated with other anxiety disorders. OBJECTIVES: The aim of this study is to review the degree of overlap between OCD and other anxiety disorders phenomenology and pathophysiology to support the rationale that guides research in this field. RESULTS: Clues about the neurocircuits involved in the manifestation of anxiety disorders have been obtained through the study of animal anxiety models, and structural and functional neuroimaging in humans. These investigations suggest that in OCD, in addition to dysfunction in cortico-striatal pathways, the functioning of an alternative neurocircuitry, which involves amygdalo-cortical interactions and participates in fear conditioning and extinction processes, may be impaired. CONCLUSION: It is likely that anxiety is a relevant dimension of OCD that impacts on other features of this disorder. Therefore, future studies may benefit from the investigation of the expression of fear and anxiety by OCD patients according to their type of obsessions and compulsions, age of OCD onset, comorbidities, and patterns of treatment response.

A ansiedade é um componente importante da psicopatologia do transtorno obsessivo-compulsivo (TOC). Até o momento, a maioria das intervenções que provaram ser eficazes para o tratamento de TOC é semelhante àquelas desenvolvidas para outros transtornos de ansiedade. No entanto, estudos que investigaram a neurobiologia do TOC chegaram a conclusões que nem sempre são compatíveis com aquelas anteriormente associadas aos demais transtornos de ansiedade. OBJETIVOS: Neste artigo, revisamos o grau de sobreposição entre as características do TOC e a fenomenologia e fisiopatologia dos demais transtornos de ansiedade com o intuito de dar suporte ao racional que orienta a pesquisa nesse campo. RESULTADOS: Alguns dados sobre os neurocircuitos envolvidos na manifestação dos transtornos de ansiedade foram obtidos a partir do estudo de modelos animais de ansiedade, e da neuroimagem estrutural e funcional em humanos. Esses trabalhos sugerem que no TOC, além da disfunção das vias corticoestriatais, o funcionamento do circuito amigdalocortical, essencial para a apresentação da resposta de medo e processos de extinção dessa resposta, também pode estar prejudicado. CONCLUSÃO: É provável que a ansiedade seja uma dimensão relevante do TOC, com impacto em outras características desse transtorno. Consequentemente, estudos futuros podem se beneficiar da investigação dos fenômenos de medo e ansiedade e de suas relações com os tipos de obsessões e compulsões, idade de início do TOC, comorbidades e padrões de resposta ao tratamento.

Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by γ-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 μL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

The influence of stress on fear memory processes

It is well recognized that stressful experiences promote robust emotional memories, which are well remembered. The amygdaloid complex, principally the basolateral complex (BLA), plays a pivotal role in fear memory and in the modulation of stress-induced emotional responses. A large number of reports have revealed that GABAergic interneurons provide a powerful inhibitory control of the activity of projecting glutamatergic neurons in the BLA. Indeed, a reduced GABAergic control in the BLA is essential for the stress-induced influence on the emergence of associative fear memory and on the generation of long-term potentiation (LTP) in BLA neurons. The extracellular signal-regulated kinase (ERK) subfamily of the mitogen-activated protein kinase (MAPK) signaling pathway in the BLA plays a central role in the consolidation process and synaptic plasticity. In support of the view that stress facilitates long-term fear memory, stressed animals exhibited a phospho-ERK2 (pERK2) increase in the BLA, suggesting the involvement of this mechanism in the promoting influence of threatening stimuli on the consolidation fear memory. Moreover, the occurrence of reactivation-induced lability is prevented when fear memory is encoded under intense stressful conditions since the memory trace remains immune to disruption after recall in previously stressed animals. Thus, the underlying mechanism in retrieval-induced instability seems not to be functional in memories formed under stress. All these findings are indicative that stress influences both the consolidation and reconsolidation fear memory processes. Thus, it seems reasonable to propose that the emotional state generated by an environmental challenge critically modulates the formation and maintenance of long-term fear memory.

On the relationships between ultrasonic calling and anxiety-related behavior in rats

In the present review, the phenomenon of ultrasonic vocalization in rats will be outlined, including the three classes of vocalizations, namely 40-kHz calls of pups, and 22- and 50-kHz calls of juvenile and adult rats, their general relevance to behavioral neuroscience, and their special relevance to research on anxiety, fear, and defense mechanisms. Here, the emphasis will be placed on 40- and 22-kHz calls, since they are typical for various situations with aversive properties. Among other topics, we will discuss whether such behavioral signals can index a certain affective state, and how these signals can be used in social neuroscience, especially with respect to communication. Furthermore, we will address the phenomenon of inter-individual variability in ultrasonic calling and what we currently know about the mechanisms, which may determine such variability. Finally, we will address the current knowledge on the neural and pharmacological mechanisms underlying 22-kHz ultrasonic vocalization, which show a substantial overlap with mechanisms known from other research on fear and anxiety, such as those involving the periaqueductal gray or the amygdala.

What ethologically based models have taught us about the neural systems underlying fear and anxiety

Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

Postural balance in patients with social anxiety disorder

Body stability is controlled by the postural system and can be affected by fear and anxiety. Few studies have addressed freezing posture in psychiatric disorders. The purpose of the present study was to assess posturographic behavior in 30 patients with social anxiety disorder (SAD) and 35 without SAD during presentation of blocks of pictures with different valences. Neutral images consisted of objects taken from a catalog of pictures, negative images were mutilation pictures and anxiogenic images were related to situations regarding SAD fears. While participants were standing on a force platform, similar to a balance, displacement of the center of pressure in the mediolateral and anteroposterior directions was measured. We found that the SAD group exhibited a lower sway area and a lower velocity of sway throughout the experiment independent of the visual stimuli, in which the phobic pictures, a stimulus associated with a defense response, were unable to evoke a significantly more rigid posture than the others. We hypothesize that patients with SAD when entering in a situation of exposure, from the moment the pictures are presented, tend to move less than controls, remaining this way until the experiment ends. This discrete body manifestation can provide additional data to the characterization of SAD and its differentiation from other anxiety disorders, especially in situations regarding facing fear.

Induction of Zenk protein expression within the nucleus taeniae of the amygdala of pigeons following tone and shock stimulation

In this study, we evaluated the expression of the Zenk protein within the nucleus taeniae of the pigeon’s amygdala (TnA) after training in a classical aversive conditioning, in order to improve our understanding of its functional role in birds. Thirty-two 18-month-old adult male pigeons (Columba livia), weighing on average 350 g, were trained under different conditions: with tone-shock associations (experimental group; EG); with shock-alone presentations (shock group; SG); with tone-alone presentations (tone group; TG); with exposure to the training chamber without stimulation (context group; CG), and with daily handling (naive group; NG). The number of immunoreactive nuclei was counted in the whole TnA region and is reported as density of Zenk-positive nuclei. This density of Zenk-positive cells in the TnA was significantly greater for the EG, SG and TG than for the CG and NG (P < 0.05). The data indicate an expression of Zenk in the TnA that was driven by experience, supporting the role of this brain area as a critical element for neural processing of aversive stimuli as well as meaningful novel stimuli.

Controle autonômico da freqüência cardíaca em Spilotes pullatus (Colubridae) como determinante das respostas de medo / Autonomic control of heart rate in Spilotes pullatus (Colubridae) as determinant of fear responses

Neste estudo, investigaram-se as modificações fisiológicas em Spilotes pullatus, como determinantes das respostas ao medo, obtidas pela exposição ao eletrocardiograma. Foram utilizadas quatro serpentes com média de peso de 0,5±0,06kg. Dois minutos após a fixação dos eletrodos, as serpentes apresentavam-se imóveis, com redução significativa na freqüência cardíaca e aumento nos intervalos PQ, QRS, RR e RT (P<0,05). Os resultados sugerem que a presença de sintomas de medo pode gerar riscos à saúde desses animais.

This study investigated electrocardiographic changes in Spilotes pullatus using four snakes weighing 0.5±0.06kg. Two minutes after that electrocardiogram apparatus had been fixed in Spilotes pullatus, snakes were immobile and there was a significant reduction of the heart rate and an increase in PQ, QRS, RR, and RT intervals (P<0.05). Results suggest that the presence of fear symptoms may represent a risk to the health of snakes.

The extinction of conditioned fear: structural and molecular basis and therapeutic use

OBJECTIVE: Through association, a large variety of stimuli acquire the property of signaling pleasant or aversive events. Pictures of a wedding or of a plane disaster may serve as cues to recall these events and/or others of a similar nature or emotional tone. Presentation of the cues unassociated with the events, particularly if repeated, reduces the tendency to retrieve the original learning based on that association. This attenuation of the expression of a learned response was discovered by Pavlov 100 years ago, who called it extinction. In this article we review some of the most recent findings about the behavioral and biochemical properties of extinction. RESULTS AND DISCUSSION: It has been shown that extinction is a new learning based on a new link formed by the cues and the absence of the original event(s) which originated the first association. Extinction does not consist of the erasure of the original memory, but of an inhibition of its retrieval: the original response reappears readily if the former association is reiterated, or if enough time is allowed to pass (spontaneous recovery). Extinction requires neural activity, signaling pathways, gene expression and protein synthesis in the ventromedial prefrontal cortex and/or basolateral amygdala, hippocampus, entorhinal cortex and eventually other areas. The site or sites of extinction vary with the task. CONCLUSIONS: Extinction was advocated by Freud in the 1920's for the treatment of phobias, and is used in cognitive therapy to treat diseases that rely on conditioned fear (phobias, panic, and particularly posttraumatic stress disorder). The treatment of learned fear disorders with medications is still unsatisfactory although some have been shown useful when used as adjuncts to behavioral therapy.

OBJETIVO: Muitos estímulos podem adquirir características prazerosas ou aversivas por meio da formação de associações. Fotografias de um casamento ou de um acidente aeronáutico podem servir como dicas para lembrar esses eventos e outros de natureza ou caráter emocional semelhante. Porém, sabe-se que a apresentação repetida de uma dica na ausência do estímulo ao qual está associada reduz a probabilidade de expressão da memória em questão. Este fenômeno de atenuação foi descoberto por Pavlov há quase 100 anos, recebendo o nome de extinção. Neste artigo de revisão, comentamos alguns dos achados mais recentes a respeito das propriedades comportamentais e bioquímicas do processo de extinção de memórias. RESULTADOS E DISCUSSÃO: Tem sido demonstrado que a extinção não envolve esquecimento, mas a inibição da expressão da memória original juntamente com um novo aprendizado, que inclui a formação de uma relação entre a dica e a ausência do estímulo que originou a primeira associação. De fato, a memória original reaparece rapidamente após a re-exposição ao estímulo adequado ou, simplesmente, com o passar do tempo (recuperação espontânea). A extinção requer atividade neural, diferente vias de sinalização neuronal, incluindo a expressão de genes e a síntese de proteínas, em diferentes áreas do cérebro. Estas variam com a tarefa, mas distintos estudos sugerem que tanto o córtex pré-frontal medial como o córtex entorrinal, a amígdala basolateral, hipocampo entre outras áreas desempenham um papel fundamental neste processo. CONCLUSÕES: Nos anos 20 do século XX, Freud recomendou a utilização de terapias baseadas na extinção para o tratamento de fobias. Hoje, a extinção é utilizada na terapia cognitiva de distintas desordens, incluindo o pânico e o estresse pós-traumático. Ainda que alguns medicamentos tenham demonstrado sua eficácia como coadjuvantes na terapia comportamental do medo aprendido, a resposta destes pacientes ao tratamento farmacológico ainda...

Neuroanatomia do transtorno de pânico / Neuroanatomy of panic disorder

OBJETIVOS: O Transtorno de Pânico (TP) é um transtorno de ansiedade que permite um estudo comparativo de modelos animais visando à elucidação dos circuitos cerebrais envolvidos na sua gênese, embora estes ainda tenham sido pouco discutidos. MÉTODOS: Os autores realizam uma revisão da literatura sobre neurobiologia e neuroanatomia do TP. RESULTADOS: Uma revisão de dados demonstra a existência de uma "rede de medo", que tem como ponto principal o núcleo central da amígdala e compreende o hipotálamo, o tálamo, o hipocampo, a substância cinzenta periaquedutal, o locus ceruleus e outras estruturas do tronco cerebral. Sua presença é evidenciada em estudos de modelos animais de estados emocionais e comportamentais, e sua presença e importância podem ser extrapoladas para o TP em humanos. CONCLUSÃO: Esta rede de medo pode permitir que novos avanços e estudos utilizando técnicas de neuroimagem e/ou psicofármacos possam auxiliar na maior elucidação da circuitos cerebrais do TP.