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.

Neural Circuit Mechanisms Involved in Animals' Detection of and Response to Visual Threats / 神经科学通报·英文版

Evading or escaping from predators is one of the most crucial issues for survival across the animal kingdom. The timely detection of predators and the initiation of appropriate fight-or-flight responses are innate capabilities of the nervous system. Here we review recent progress in our understanding of innate visually-triggered defensive behaviors and the underlying neural circuit mechanisms, and a comparison among vinegar flies, zebrafish, and mice is included. This overview covers the anatomical and functional aspects of the neural circuits involved in this process, including visual threat processing and identification, the selection of appropriate behavioral responses, and the initiation of these innate defensive behaviors. The emphasis of this review is on the early stages of this pathway, namely, threat identification from complex visual inputs and how behavioral choices are influenced by differences in visual threats. We also briefly cover how the innate defensive response is processed centrally. Based on these summaries, we discuss coding strategies for visual threats and propose a common prototypical pathway for rapid innate defensive responses.

Discrimination of anxiety- versus panic-like behavior in the wall lizard Tropidurus oreadicus

A behavioral test battery is proposed for wall lizards (Tropidurus oreadicus) that consists of inducing tonic immobility (TI) followed by post-TI behavioral scoring. After the induction of TI, the usual behavioral sequence was flight followed by freezing and tongue-flicking and/or thigmotaxis, with flight being more probable than freezing. These sequences were not observed after restraint in a normal upward position (which induced freezing but not TI) or after handling (which increased the probability of tongue-flicking). Alprazolam and imipramine selectively decreased the duration of TI as well as the following flight and freezing behavior. Tongue-flicking was increased by diazepam and alprazolam, whereas fluoxetine decreased it. Finally, thigmotaxis was reduced by diazepam, alprazolam, and imipramine but increased by fluoxetine. These results suggest that panic and anxiety can be discriminated pharmacologically in wall lizards...

Contrasting effects of nitric oxide and corticotropin- releasing factor within the dorsal periaqueductal gray on defensive behavior and nociception in mice

The anxiogenic and antinociceptive effects produced by glutamate N-methyl-D-aspartate receptor activation within the dorsal periaqueductal gray (dPAG) matter have been related to nitric oxide (NO) production, since injection of NO synthase (NOS) inhibitors reverses these effects. dPAG corticotropin-releasing factor receptor (CRFr) activation also induces anxiety-like behavior and antinociception, which, in turn, are selectively blocked by local infusion of the CRF type 1 receptor (CRFr1) antagonist, NBI 27914 [5-chloro-4-(N-(cyclopropyl)methyl-N-propylamino)-2-methyl-6-(2,4,6-trichlorophenyl)aminopyridine]. Here, we determined whether i) the blockade of the dPAG by CRFr1 attenuates the anxiogenic/antinociceptive effects induced by local infusion of the NO donor, NOC-9 [6-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hexanamine], and ii) the anxiogenic/antinociceptive effects induced by intra-dPAG CRF are prevented by local infusion of Nω-propyl-L-arginine (NPLA), a neuronal NOS inhibitor, in mice. Male Swiss mice (12 weeks old, 25-35 g, N = 8-14/group) were stereotaxically implanted with a 7-mm cannula aimed at the dPAG. Intra-dPAG NOC-9 (75 nmol) produced defensive-like behavior (jumping and running) and antinociception (assessed by the formalin test). Both effects were reversed by prior local infusion of NBI 27914 (2 nmol). Conversely, intra-dPAG NPLA (0.4 nmol) did not modify the anxiogenic/antinociceptive effects of CRF (150 pmol). These results suggest that CRFr1 plays an important role in the defensive behavior and antinociception produced by NO within the dPAG. In contrast, the anxiogenic and antinociceptive effects produced by intra-dPAG CRF are not related to NO synthesis in this limbic midbrain structure.

Modulation of nociceptive-like behavior in zebrafish (Danio rerio) by environmental stressors

Zebrafish have been demonstrated to react consistently to noxious chemical stimuli and present reliable phenotypes of stress, fear, and anxiety. In this article, we describe the modulation of nociceptive-like responses of zebrafish to fear-, stress-, and anxiety-eliciting situations. Animals were exposed to an alarm substance, confinement stress, or a novel environment before being injected with 1 percent acetic acid in the tail. The alarm substance and confinement stress reduced the display of erratic movements and tail-beating behavior elicited by acetic acid. The novelty of the environment, in contrast, increased the frequency of tail-beating behavior. The results suggest that descending modulatory control of nociception exists in zebrafish, with apparent fear- and stress-induced analgesia and anxiety-induced hyperalgesia.

Effects of contextual fear conditioning and pentylenetetrazol on panic-like reactions induced by dorsal periaqueductal gray stimulation with N-methyl-D-aspartate

Electrical or chemical stimulation of the dorsal periaqueductal gray (DPAG) has been accepted as an animal model of panic attacks. This study investigates the influence of anticipatory anxiety in the occurrence of panic-like behavior induced by N-methyl-D-aspartate (NMDA) microinjection into the DPAG of rats. Behavioral (i.e., contextual fear conditioning) and pharmacological (i.e., pentylenetetrazol) manipulations were employed as animal models of anticipatory anxiety. In the first experiment, animals exposed to contextual cues that had been previously associated with electric footshocks through contextual fear conditioning were less likely than non-conditioned control animals to display defensive reactions such as running and jumping in response to microinjection of NMDA (0.3 µl of 15.0 µg/µl) into the DPAG. In the second experiment, rats were injected intraperitoneally with the anxiogenic drug pentylenetetrazol (PTZ, 15 mg/kg) 5 minutes before receiving intra-DPAG microinfusion with the same dose of NMDA as in Experiment 1. Panic-related behaviors were registered in an experimental arena immediately after NMDA microinfusion. As compared with saline pre-treated animals, PTZ significantly attenuated NMDA-induced panic-like reactions. These results further demonstrate the usefulness of DPAG chemical stimulation as an animal model of panic attacks and suggest that behavioral and pharmacological activation of the brain mechanisms underlying anticipatory anxiety might exert an antipanic-like effect.

Catalepsia induzida pelo lactato e atividade muscular forçada em ratos privados de sono / Catalepsy induced by lactate administration and forced muscular activity in rats

O estudo comparativo das homologias comportamentais é útil para a compreensão de diferentes aspectos dos transtornos psiquiátricos. Nesta perspectiva, o presente estudo avaliou os efeitos da privação de sono REM sobre a catalepsia. Ratos privados de sono REM por 4 dias foram submetidos à administração i.p. de lactato 10mM/Kg e exercício muscular forçado, sendo, então a catalepsia avaliada. O grupo de animais privados de sono mostrou menor incidência (50 por cento) de animais com catalepsia e média do tempo total de catalepsia menor (11,92 ± 4,12 minutos) em relação aos controles (91,7 por cento e 26,67 ± 5,86 min respectivamente), com significâncias estatísticas no limite (p=0,05). Conclui-se que, em uma situação de perigo prolongado, a catalepsia é disparada em uma segunda instância, após o esgotamento do repertório de enfrentamentos normais da vigília, e que o sono só é compensado após o término da situação de risco

Comparative studies of behavioral homologies help understand several aspects of psychiatric disorders. The present study evaluated the effect of REM-sleep deprivation on the catalepsy induced by lactate administration plus forced muscular activity. Rats deprived of REM-sleep for 96 hs were injected i.p. with lactate solution 10mM/kg and submitted to 5 minutes of forced muscular activity. Catalepsy was then evaluated. The number of animals displaying catalepsy (50%) and mean total catalepsy time (11,92 ± 4,12 minutes) were lower in sleep deprived animals than in controls (91.7% and 26.67 ± 5.86 min respectively), results being statistically significant at the limit level (p=0,05). It is concluded that in long lasting dangerous situations, catalepsy may be triggered after normal wakefulness coping possibilities are exhausted, and sleep being manifested only when the risk situation is over.

Defensive repertoire of Xenodon dorbignyi (Serpentes, Dipsadidae) / Repertório defensivo de Xenodon dorbignyi (Serpentes, Dipsadidae)

The ability of a species to defend itself against a predator is directly correlated with its survivorship. Thus, prey/predator interaction mechanisms are important elements of the natural history of species. In this study, we examined the defensive repertoire of the South-American hognose snake (Xenodon dorbignyi) through simulations of predator attacks in the field. Nine defensive displays were observed. The most frequently observed displays were erratic movements, body flattening, head triangulation and tail display. No differences were detected in the defensive strategies shown by males and females, regardless of their reproductive state. Our findings suggest that X. dorbignyi has the ability to evaluate the level of threat imposed by the aggressor, with cryptic behavior, body flattening and locomotor escape as the primary defensive strategies, with other displays used as secondary responses to a predator attack. Our results support the hypothesis that X. dorbignyi is a mimic of both Micrurus and Bothrops.

A capacidade de uma espécie em defender-se da ação de um predador esta diretamente relacionada à sua sobrevivência. Nesse sentido, os mecanismos de interação presa/predador são elementos importantes da história natural das espécies. Neste estudo foi avaliado o repertório defensivo da cobra-nariguda (Xenodon dorbignyi), a partir da simulação de ataques predatórios na natureza. Foram observadas nove unidades comportamentais defensivas, sendo os movimentos erráticos, achatamento do corpo, triangulação da cabeça e display caudal os comportamentos mais freqüentemente exibidos. Não foram detectadas diferenças na estratégia defensiva entre os sexos ou entre indivíduos em diferentes estados reprodutivos. Os resultados sugerem que X. dorbignyi possui a capacidade de avaliar o nível de ameaça imposto pelo agressor, sendo o comportamento críptico, o achatamento do corpo e a fuga as estratégias defensivas primárias, com os demais displays representando respostas secundárias ao ataque predatório. Os resultados reforçam a hipótese de que X. dorbignyi represente simultaneamente um mímico de Micrurus e Bothrops.

Serotonergic modulation of face-emotion recognition: [review]

Facial expressions of basic emotions have been widely used to investigate the neural substrates of emotion processing, but little is known about the exact meaning of subjective changes provoked by perceiving facial expressions. Our assumption was that fearful faces would be related to the processing of potential threats, whereas angry faces would be related to the processing of proximal threats. Experimental studies have suggested that serotonin modulates the brain processes underlying defensive responses to environmental threats, facilitating risk assessment behavior elicited by potential threats and inhibiting fight or flight responses to proximal threats. In order to test these predictions about the relationship between fearful and angry faces and defensive behaviors, we carried out a review of the literature about the effects of pharmacological probes that affect 5-HT-mediated neurotransmission on the perception of emotional faces. The hypothesis that angry faces would be processed as a proximal threat and that, as a consequence, their recognition would be impaired by an increase in 5-HT function was not supported by the results reviewed. In contrast, most of the studies that evaluated the behavioral effects of serotonin challenges showed that increased 5-HT neurotransmission facilitates the recognition of fearful faces, whereas its decrease impairs the same performance. These results agree with the hypothesis that fearful faces are processed as potential threats and that 5-HT enhances this brain processing.

The defensive strike of five species of lanceheads of the genus Bothrops (Viperidae)

We studied the defensive strike of one species of each of five recognized lineages within the genus Bothrops, namely, B. alternatus, B. jararaca, B. jararacussu, B. moojeni and B. pauloensis. The defensive strike of the studied species was in general similar to that of Crotalus viridis and C. atrox, but some important differences were observed. Bothrops alternatus and B. pauloensis struck preferentially from a tight body posture, whereas B. jararaca and B. moojeni from a loose body posture. Defensive strikes were either true or false (during the latter, the mouth remains closed or partially open). Almost all strikes were successful; only on a few occasions snakes missed their target (flawed strikes). Strike variables were very conservative among the five species, especially strike distance and height, and one possible explanation may be related to constraints imposed on strike variables as a way of increasing strike accuracy.

Estudamos o bote defensivo de uma espécie de cada uma de cinco reconhecidas linhagens do gênero Bothrops, a saber: B. alternatus, B. jararaca, B. jararacussu, B. moojeni e B. pauloensis. O bote defensivo das espécies estudadas foi, em geral, semelhante ao de Crotalus viridis e C. atrox, porém algumas diferenças foram observadas. Bothrops alternatus e B. pauloensis desferiram botes preferencialmente a partir de postura corpórea enrodilhada, ao passo que B. jararaca e B. moojeni desferiram a maioria dos botes a partir de postura corpórea frouxa. Os botes defensivos foram verdadeiros ou falsos (nestes, a boca da serpente permaneceu fechada ou parcialmente aberta). Quase todos os botes foram bem-sucedidos; apenas em alguns casos a serpente errou o alvo (botes falhos). As variáveis relativas aos botes foram bastante conservativas entre as cinco espécies, principalmente distância e altura do bote, e uma possível explicação pode estar relacionada a restrições impostas às variáveis relativas aos botes como forma de aumentar sua acurácia.