RESUMO
In this study, we have aimed at outlining the neural systems underlying the expression of contextual fear to social defeat. First, we have developed an experimental procedure, where defeated animals could express, without the presence of a dominant aggressive male, robust and reliable conditioned fear responses to the context associated with social defeat. Next, by examining the pattern of Fos expression, we have been able to outline a brain circuit comprising septal and amygdalar sites, as well as downstream hypothalamic paths, putatively involved in the expression of contextual fear to social threat. Of particular relevance, we have found that exposure to a defeat-associated context results in a striking Fos up-regulation in the dorsomedial part of the dorsal premammillary nucleus (PMDdm). To further understand the role of the PMDdm in the circuit organizing conditioned fear to social threats, we have been able to observe that pharmacological blockade of the PMDdm reduced fear responses to a social defeat-associated context. Next, we observed that pharmacological blockade of the dorsomedial part of the periaqueductal gray, one of the main targets of the PMDdm, produced an even higher reduction of conditioned fear in defeated intruders, and appears as an important node for the expression of contextual defensive responses to social threats. The present results help to elucidate the basic organization of the neural circuits underlying contextual conditioned responses to social defeat, and reveal that they share at least part of the same circuit involved in innate responses to social defeat to an aggressive conspecific.
Assuntos
Tonsila do Cerebelo/fisiologia , Comportamento Animal/fisiologia , Mapeamento Encefálico , Medo/fisiologia , Hipotálamo/fisiologia , Vias Neurais/fisiologia , Animais , Condicionamento Psicológico/fisiologia , Masculino , Substância Cinzenta Periaquedutal/fisiologia , Ratos WistarRESUMO
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.
Assuntos
Animais , Tonsila do Cerebelo/fisiologia , Ansiedade/fisiopatologia , Condicionamento Psicológico/fisiologia , Medo/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Ansiedade/psicologia , Modelos Animais de Doenças , Medo/psicologia , Modelos Neurológicos , Vias Neurais/fisiologiaRESUMO
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.
Assuntos
Tonsila do Cerebelo/fisiologia , Ansiedade/fisiopatologia , Condicionamento Psicológico/fisiologia , Medo/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Animais , Ansiedade/psicologia , Modelos Animais de Doenças , Medo/psicologia , Modelos Neurológicos , Vias Neurais/fisiologiaRESUMO
Opioid peptides play an important role in maternal behaviour, as well as in physiological and pathological phenomena involving motivation. Daily 3.5 mg/kg doses of morphine from days 17-21 of pregnancy are able to change the expression of maternal behaviour patterns. However, the role of hormones on such opioid behavioural actions remains to be determined. The present study investigated the endocrine responses to this morphine treatment. Corticosterone, progesterone, oestradiol and prolactin serum concentrations were measured after each morphine injection. No significant differences were found in corticosterone, oestradiol or prolactin serum concentrations. The results suggest that the treatment was unable to promote different effects, other than those caused by saline injections. In morphine-treated animals, however, progesterone concentrations were consistently and significantly increased from days 18-20 of treatment. Thus, because this behavioural meaningful opioidergic stimulation during late pregnancy affects progesterone levels, the findings of the present study raise the hypothesis that this hormone may play a role in morphine-induced changes in opioid sensitivity during late pregnancy and early lactation.
Assuntos
Morfina/farmacologia , Peptídeos Opioides/farmacologia , Período Pós-Parto , Progesterona/fisiologia , Animais , Feminino , Masculino , RadioimunoensaioRESUMO
The amygdala plays a critical role in determining the emotional significance of sensory stimuli and the production of fear-related responses. Large amygdalar lesions have been shown to practically abolish innate defensiveness to a predator; however, it is not clear how the different amygdalar systems participate in the defensive response to a live predator. Our first aim was to provide a comprehensive analysis of the amygdalar activation pattern during exposure to a live cat and to a predator-associated context. Accordingly, exposure to a live predator up-regulated Fos expression in the medial amygdalar nucleus (MEA) and in the lateral and posterior basomedial nuclei, the former responding to predator-related pheromonal information and the latter two nuclei likely to integrate a wider array of predatory sensory information, ranging from olfactory to non-olfactory ones, such as visual and auditory sensory inputs. Next, we tested how the amygdalar nuclei most responsive to predator exposure (i.e. the medial, posterior basomedial and lateral amygdalar nuclei) and the central amygdalar nucleus (CEA) influence both unconditioned and contextual conditioned anti-predatory defensive behavior. Medial amygdalar nucleus lesions practically abolished defensive responses during cat exposure, whereas lesions of the posterior basomedial or lateral amygdalar nuclei reduced freezing and increased risk assessment displays (i.e. crouch sniff and stretch postures), a pattern of responses compatible with decreased defensiveness to predator stimuli. Moreover, the present findings suggest a role for the posterior basomedial and lateral amygdalar nuclei in the conditioning responses to a predator-related context. We have further shown that the CEA does not seem to be involved in either unconditioned or contextual conditioned anti-predatory responses. Overall, the present results help to clarify the amygdalar systems involved in processing predator-related sensory stimuli and how they influence the expression of unconditioned and contextual conditioned anti-predatory responses.
Assuntos
Tonsila do Cerebelo/fisiologia , Comportamento Animal/fisiologia , Condicionamento Psicológico/fisiologia , Medo/fisiologia , Comportamento Predatório/fisiologia , Tonsila do Cerebelo/anatomia & histologia , Animais , Gatos , Ambiente Controlado , Abrigo para Animais/normas , Masculino , Estimulação Luminosa/métodos , Ratos , Ratos WistarRESUMO
It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.
Assuntos
Animais , Feminino , Masculino , Ratos , Comportamento Materno/efeitos dos fármacos , Morfina/farmacologia , Entorpecentes/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Animais Recém-Nascidos , Comportamento Materno/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Ratos Wistar , Tempo de Reação/efeitos dos fármacosRESUMO
It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.
Assuntos
Comportamento Materno/efeitos dos fármacos , Morfina/farmacologia , Entorpecentes/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Feminino , Masculino , Comportamento Materno/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacosRESUMO
Combining the results of behavioral, neuronal immediate early gene activation, lesion and neuroanatomical experiments, we have presently investigated the role of the superior colliculus (SC) in predatory hunting. First, we have shown that insect hunting is associated with a characteristic large increase in Fos expression in the lateral part of the intermediate gray layer of the SC (SCig). Next, we have shown that animals with bilateral NMDA lesions of the lateral parts of the SC presented a significant delay in starting to chase the prey and longer periods engaged in other activities than predatory hunting. They also showed a clear deficit to orient themselves toward the moving prey and lost the stereotyped sequence of actions seen for capturing, holding and killing the prey. Our Phaseolus vulgaris-leucoagglutinin analysis revealed that the lateral SCig, besides providing the well-documented descending crossed pathway to premotor sites in brainstem and spinal cord, projects to a number of midbrain and diencephalic sites likely to influence key functions in the context of the predatory behavior, such as general levels of arousal, motivational level to hunt or forage, behavioral planning, appropriate selection of the basal ganglia motor plan to hunt, and motor output of the primary motor cortex. In contrast to the lateral SC lesions, medial SC lesions produced a small deficit in predatory hunting, and compared to what we have seen for the lateral SCig, the medial SCig has a very limited set of projections to thalamic sites related to the control of motor planning or motor output, and provides conspicuous inputs to brainstem sites involved in organizing a wide range of anti-predatory defensive responses. Overall, the present results served to clarify how the different functional domains in the SC may mediate the decision to pursue and hunt a prey or escape from a predator.
Assuntos
Comportamento Predatório/fisiologia , Colículos Superiores/fisiologia , Animais , Reação de Fuga/fisiologia , Masculino , Proteínas Proto-Oncogênicas c-fos/biossíntese , Ratos , Ratos WistarRESUMO
In this study we provide a comprehensive analysis of the hypothalamic activation pattern during exposure to a live predator or an environment previously associated with a predator. Our results support the view that hypothalamic processing of the actual and the contextual predatory threats share the same circuit, in which the dorsal premammillary nucleus (PMd) plays a pivotal role in amplifying this processing. To further understand the role of the PMd in the circuit organizing antipredatory defensive behaviors, we studied rats with cytotoxic PMd lesions during cat exposure and examined the pattern of behavioral responses as well as how PMd lesions affect the neuronal activation of the systems engaged in predator detection, in contextual memory formation and in defensive behavioral responses. Next, we investigated how pharmacological blockade of the PMd interferes with the conditioned behavioral responses to a context previously associated with a predator, and how this blockade affects the activation pattern of periaqueductal gray (PAG) sites likely to organize the conditioned behavioral responses to the predatory context. Behavioral observations indicate that the PMd interferes with both unconditioned and conditioned antipredatory defensive behavior. Moreover, we have shown that the PMd influences the activation of its major projecting targets, i.e. the ventral part of the anteromedial thalamic nucleus which is likely to influence mnemonic processing, and PAG sites involved in the expression of antipredatory unconditioned and conditioned behavioral responses. Of particular relevance, this work provides evidence to elucidate the basic organization of the neural circuits integrating unconditioned and contextual conditioned responses to predatory threats.
Assuntos
Comportamento Animal/fisiologia , Condicionamento Psicológico/fisiologia , Medo/fisiologia , Hipotálamo/anatomia & histologia , Hipotálamo/fisiologia , Animais , Núcleos Anteriores do Tálamo/anatomia & histologia , Núcleos Anteriores do Tálamo/fisiologia , Mapeamento Encefálico , Gatos , Denervação , Agonistas GABAérgicos/farmacologia , Masculino , Corpos Mamilares/anatomia & histologia , Corpos Mamilares/fisiologia , Memória/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Testes Neuropsicológicos , Neurotoxinas/farmacologia , Substância Cinzenta Periaquedutal/anatomia & histologia , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos Wistar , Estresse Psicológico/fisiopatologiaRESUMO
The architecture of the amygdaloid complex of a marsupial, the opossum Didelphis aurita, was analyzed using classical stains like Nissl staining and myelin (Gallyas) staining, and enzyme histochemistry for acetylcholinesterase and NADPH-diaphorase. Most of the subdivisions of the amygdaloid complex described in eutherian mammals were identified in the opossum brain. NADPH-diaphorase revealed reactivity in the neuropil of nearly all amygdaloid subdivisions with different intensities, allowing the identification of the medial and lateral subdivisions of the cortical posterior nucleus and the lateral subdivision of the lateral nucleus. The lateral, central, basolateral and basomedial nuclei exhibited acetylcholinesterase positivity, which provided a useful chemoarchitectural criterion for the identification of the anterior basolateral nucleus. Myelin stain allowed the identification of the medial subdivision of the lateral nucleus, and resulted in intense staining of the medial subdivisions of the central nucleus. The medial, posterior, and cortical nuclei, as well as the amygdalopiriform area did not exhibit positivity for myelin staining. On the basis of cyto- and chemoarchitectural criteria, the present study highlights that the opossum amygdaloid complex shares similarities with that of other species, thus supporting the idea that the organization of the amygdala is part of a basic plan conserved through mammalian evolution.