Project description:Much of brain science is concerned with understanding the neural circuits that underlie specific behaviors. While the mouse has become a favorite experimental subject, the behaviors of this species are still poorly explored. For example, the mouse retina, like that of other mammals, contains ?20 different circuits that compute distinct features of the visual scene [1, 2]. By comparison, only a handful of innate visual behaviors are known in this species--the pupil reflex [3], phototaxis [4], the optomotor response [5], and the cliff response [6]--two of which are simple reflexes that require little visual processing. We explored the behavior of mice under a visual display that simulates an approaching object, which causes defensive reactions in some other species [7, 8]. We show that mice respond to this stimulus either by initiating escape within a second or by freezing for an extended period. The probability of these defensive behaviors is strongly dependent on the parameters of the visual stimulus. Directed experiments identify candidate retinal circuits underlying the behavior and lead the way into detailed study of these neural pathways. This response is a new addition to the repertoire of innate defensive behaviors in the mouse that allows the detection and avoidance of aerial predators.
Project description:The neural circuit mechanisms underlying emotion states remain poorly understood. Drosophila offers powerful genetic approaches for dissecting neural circuit function, but whether flies exhibit emotion-like behaviors has not been clear. We recently proposed that model organisms may express internal states displaying "emotion primitives," which are general characteristics common to different emotions, rather than specific anthropomorphic emotions such as "fear" or "anxiety." These emotion primitives include scalability, persistence, valence, and generalization to multiple contexts. Here, we have applied this approach to determine whether flies' defensive responses to moving overhead translational stimuli ("shadows") are purely reflexive or may express underlying emotion states. We describe a new behavioral assay in which flies confined in an enclosed arena are repeatedly exposed to an overhead translational stimulus. Repetitive stimuli promoted graded (scalable) and persistent increases in locomotor velocity and hopping, and occasional freezing. The stimulus also dispersed feeding flies from a food resource, suggesting both negative valence and context generalization. Strikingly, there was a significant delay before the flies returned to the food following stimulus-induced dispersal, suggestive of a slowly decaying internal defensive state. The length of this delay was increased when more stimuli were delivered for initial dispersal. These responses can be mathematically modeled by assuming an internal state that behaves as a leaky integrator of stimulus exposure. Our results suggest that flies' responses to repetitive visual threat stimuli express an internal state exhibiting canonical emotion primitives, possibly analogous to fear in mammals. The mechanistic basis of this state can now be investigated in a genetically tractable insect species.
Project description:Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the development and function of these circuits remain unresolved. Here we show that midbrain-specific deletion of the transcription factor Brn3b causes a loss of neurons projecting to the lateral posterior nucleus of the thalamus. Brn3b deletion also downregulates the expression of the neuropeptide tachykinin 2 (Tac2). Furthermore, Brn3b mutant mice display impaired defensive freezing responses to visual threat precipitated by social isolation. This behavioral phenotype could be ameliorated by overexpressing Tac2, suggesting that Tac2 acts downstream of Brn3b in regulating defensive responses to threat. Together, our experiments identify specific genetic components critical for the functional organization of midbrain fear-related visual circuits. Similar mechanisms may contribute to the development and function of additional long-range brain circuits underlying fear-associated behavior.
Project description:The defensive peripersonal space (DPPS) is a vital "safety margin" surrounding the body. When a threatening stimulus is delivered inside the DPPS, subcortical defensive responses like the hand-blink reflex (HBR) are adjusted depending on the perceived threat content. In three experiments, we explored whether and how defensive responses are affected by the interpersonal interaction within the DPPS of the face. In Experiment 1, we found that the HBR is enhanced when the threat is brought close to the face not only by one's own stimulated hand, but also by another person's hand, although to a significantly lesser extent. In Experiments 2 and 3, we found that the HBR is also enhanced when the hand of the participant enters the DPPS of another individual, either in egocentric or in allocentric perspective. This enhancement is larger in participants with strong empathic tendency when the other individual is in a third person perspective. These results indicate that interpersonal interactions shape perception of threat and defensive responses. These effects are particularly evident in individuals with greater tendency to having empathic concern to other people.
Project description:The ventral tegmental area (VTA) has dopamine, GABA, and glutamate neurons, which have been implicated in reward and aversion. Here, we determined whether VTA-glutamate or -GABA neurons play a role in innate defensive behavior. By VTA cell-type-specific genetic ablation, we found that ablation of glutamate, but not GABA, neurons abolishes escape behavior in response to threatening stimuli. We found that escape behavior is also decreased by chemogenetic inhibition of VTA-glutamate neurons and detected increases in activity in VTA-glutamate neurons in response to the threatening stimuli. By ultrastructural and electrophysiological analysis, we established that VTA-glutamate neurons receive a major monosynaptic glutamatergic input from the lateral hypothalamic area (LHA) and found that photoinhibition of this input decreases escape responses to threatening stimuli. These findings indicate that VTA-glutamate neurons are activated by and required for innate defensive responses and that information on threatening stimuli to VTA-glutamate neurons is relayed by LHA-glutamate neurons.
Project description:Prior work in our lab has shown that an expanding image on a computer screen elicits a hiding response in the Caribbean terrestrial hermit crab (Coenobita clypeatus). We conducted two experiments to identify what properties of the expanding stimulus contribute to its effectiveness as a visual threat. First we found that an expanding geometric star evoked a strong hiding response while a contracting or full-sized stationary star did not. A second experiment revealed that the more quickly the stimulus expanded the shorter the latency to hide. These findings suggest that the anti-predator response to looming stimulus relies heavily on visual cues relating to the manner of approach. The simulated visual threat on a computer screen captures key features of a real looming object that elicits hiding behavior in crabs in the wild.
Project description:In humans and other mammals, defensive responses to danger vary with threat imminence, but it is unknown how those responses affect decisions to help conspecifics. Here, we manipulated threat imminence to investigate the impact of different defensive states on human helping behaviour. Ninety-eight healthy adult participants made trial-by-trial decisions about whether to help a co-participant avoid an aversive shock, at the risk of receiving a shock themselves. Helping decisions were prompted under imminent or distal threat, based on temporal distance to the moment of shock administration to the co-participant. Results showed that, regardless of how likely participants were to also receive a shock, they helped the co-participant more under imminent than distal threat. Reaction times and cardiac changes during the task supported the efficacy of the threat imminence manipulation in eliciting dissociable defensive states, with faster responses and increased heart rate during imminent compared to distal threats. Individual differences in empathic concern were specifically correlated with helping during imminent threats. These results suggest that defensive states driving active escape from immediate danger may also facilitate decisions to help others, potentially by engaging neurocognitive systems implicated in caregiving across mammals.
Project description:Postencounter and circa-strike defensive contexts represent two adaptive responses to potential and imminent danger. In the context of a predator, the postencounter reflects the initial detection of the potential threat, whereas the circa-strike is associated with direct predatory attack. We used functional magnetic resonance imaging to investigate the neural organization of anticipation and avoidance of artificial predators with high or low probability of capturing the subject across analogous postencounter and circa-strike contexts of threat. Consistent with defense systems models, postencounter threat elicited activity in forebrain areas, including subgenual anterior cingulate cortex (sgACC), hippocampus, and amygdala. Conversely, active avoidance during circa-strike threat increased activity in mid-dorsal ACC and midbrain areas. During the circa-strike condition, subjects showed increased coupling between the midbrain and mid-dorsal ACC and decreased coupling with the sgACC, amygdala, and hippocampus. Greater activity was observed in the right pregenual ACC for high compared with low probability of capture during circa-strike threat. This region showed decreased coupling with the amygdala, insula, and ventromedial prefrontal cortex. Finally, we found that locomotor errors correlated with subjective reports of panic for the high compared with low probability of capture during the circa-strike threat, and these panic-related locomotor errors were correlated with midbrain activity. These findings support models suggesting that higher forebrain areas are involved in early-threat responses, including the assignment and control of fear, whereas imminent danger results in fast, likely "hard-wired," defensive reactions mediated by the midbrain.
Project description:How humans react to threats is a topic of broad theoretical importance, and also relevant for understanding anxiety disorders. Many animal threat reactions exhibit a common structure, a finding supported by human evaluations of written threat scenarios that parallel patterns of rodent defensive behavior to actual threats. Yet the factors that underlie these shared behavioral patterns remain unclear. Dimensional accounts rooted in Darwin's conception of antithesis explain many defensive behaviors. Across species, it is also clear that defensive reactions depend on specific situational factors, a feature long emphasized by psychological appraisal theories. Our study sought to extend prior investigations of human judgments of threat to a broader set of threats, including natural disasters, threats from animals, and psychological (as opposed to physical) threats. Our goal was to test whether dimensional and specific patterns of threat evaluation replicate across different threat classes. 85 healthy adult subjects selected descriptions of defensive behaviors that indicated how they would react to 29 threatening scenarios. Scenarios differed with respect to ten factors, e.g., perceived dangerousness or escapability. Across scenarios, we correlated these factor ratings with the pattern of defensive behaviors subjects endorsed. A decision tree hierarchically organized these correlation patterns to successfully predict each scenario's most common reaction, both for the original sample of subjects and a separate replication group (n = 22). At the top of the decision tree, degree of dangerousness interacted with threat type (physical or psychological) to predict dimensional approach/avoidance behavior. Subordinate nodes represented specific defensive responses evoked by particular contexts. Our ecological approach emphasizes the interplay of situational factors in evoking a broad range of threat reactions. Future studies could test predictions made by our results to help understand pathological threat processing, such as seen in anxiety disorders, and could begin to test underlying neural mechanisms.
Project description:Successful responding to acutely threatening situations requires adequate approach-avoidance decisions. However, it is unclear how threat-induced states-like freezing-related bradycardia-impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach-avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia (high-vs-low threat) interacted with subjective value, depending on the action-context (passive-vs-active). Specifically, in action-contexts incongruent with participants' intrinsic action-tendencies, stronger bradycardia related to diminished effects of subjective value on choice across participants. These findings illustrate the relevance of testing approach-avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach-avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporating internal psychophysiological states and external action-contexts into models of approach-avoidance decision-making.