Ventromedial hypothalamic neurons control a defensive emotion state

Kunwar, Prabhat S.; Zelikowsky, Moriel; Remedios, Ryan; Cai, Haijiang; Yilmaz, Melis; Meister, Markus; Anderson, David J.

doi:10.7554/elife.06633

Cited by 968 publications

(212 citation statements)

References 124 publications

(251 reference statements)

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“…These three highly interconnected nuclei are selectively recruited by predator exposure (and not by conspecific threat or pain), receive inputs from sensory circuits detecting predatory cues, and target defense output structures like the PAG (Canteras 2002). Accordingly, inhibition of these nuclei impairs defensive responses to predators while their artificial activation promotes defensive responses in both rodents and primates (Lipp and Hunsperger 1978;Canteras et al 1997;Blanchard et al 2005;Wilent et al 2010;Pavesi et al 2011;Silva et al 2013;Kunwar et al 2015;Wang et al 2015).…”

Section: The Predator Fear Circuitmentioning

confidence: 99%

“…Nevertheless, it is important to note that even if the MHDS plays a central role in integrating predator fear, anti-predator defense can, in some specific cases, rely on alternative circuits bypassing the hypothalamus (Kunwar et al 2015). For instance, rapid responses to looming stimuli seem to rely on more direct inputs to PAG from SC (Zhao et al 2014;Shang et al 2015) and ultrasound-induce defensive responses may rely mainly on circuits centered in the IC .…”

Section: The Predator Fear Circuitmentioning

confidence: 99%

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The neural circuits of innate fear: detection, integration, action, and memorization

2016

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How fear is represented in the brain has generated a lot of research attention, not only because fear increases the chances for survival when appropriately expressed but also because it can lead to anxiety and stress-related disorders when inadequately processed. In this review, we summarize recent progress in the understanding of the neural circuits processing innate fear in rodents. We propose that these circuits are contained within three main functional units in the brain: a detection unit, responsible for gathering sensory information signaling the presence of a threat; an integration unit, responsible for incorporating the various sensory information and recruiting downstream effectors; and an output unit, in charge of initiating appropriate bodily and behavioral responses to the threatful stimulus. In parallel, the experience of innate fear also instructs a learning process leading to the memorization of the fearful event. Interestingly, while the detection, integration, and output units processing acute fear responses to different threats tend to be harbored in distinct brain circuits, memory encoding of these threats seems to rely on a shared learning system.

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Section: The Predator Fear Circuitmentioning

confidence: 99%

Section: The Predator Fear Circuitmentioning

confidence: 99%

The neural circuits of innate fear: detection, integration, action, and memorization

2016

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“…While the continuum of defensive behaviors are most easily described in terms of physical distance between predator and prey Blanchard et al 1989), behaviors within each mode increase as shock density increases, up to a point at which the mode of defense changes and the next set of behaviors emerges (Fanselow 1989;Helmstetter and Fanselow 1993). Therefore, responses may actually be controlled by different levels of a single construct (i.e., different levels of imminence), where intensity is read out as different behaviors (Kunwar et al 2015). It should be noted that Predatory Imminence Theory is an example of a more general approach called functional behavior systems, that has been successfully applied to the motivation for food and sex (Domjan 1994;Fanselow 1994;Timberlake 1994;Timberlake and Fanselow 1994).…”

Section: Predatory Imminence Theorymentioning

confidence: 99%

Neurobehavioral perspectives on the distinction between fear and anxiety

2015

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In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the neurobiological literature. A strong distinction should specify the difference in conditions that lead to fear versus anxiety. Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally, the two states should be supported by distinguishable neuroanatomical circuits. Such a conceptualization would be consistent with the National Institute of Mental Health's Research Domain Criteria (RDoc). The majority of neurobiological approaches to the fear versus anxiety distinction fail to differentiate the two states in terms of behavior, often using the exact same behavioral measures as indicators. Of the two that do, only Predatory Imminence Theory provides a distinction both in terms of cause and effect. Indeed, that approach provides a ready distinction of anxiety, fear, and panic in terms of both antecedent conditions and response selection rules. Additionally, it appeals to distinct neural circuits to generate these modes of action.Clear definitional distinctions between fear and anxiety have been elusive. There is also ambiguity in relating clinical classifications to preclinical laboratory models. The intention of this review is to describe and evaluate several neurobehavioral approaches to the distinction between fear and anxiety. A clear, research-based definition of fear and anxiety should help clarify the natural function of these brain states and point to how their dysfunction manifests as particular anxiety disorders. This relationship is becoming increasingly important with the National Institute of Mental Health's adoption of Research Domain Criteria (RDoc), which specifically attempts to link preclinical research with clinical phenomenology. The purpose of the RDoc systems is to ". . .to translate rapid progress in basic neurobiological and behavioral research to an improved integrative understanding of psychopathology and the development of new and/or optimally matched treatments for mental disorders" (National Institute of Mental Health 2013).To accomplish this goal, we will first consider the characteristics of a good definitional distinction between fear and anxiety. Then, after briefly reviewing the circuitry responsible for fear and anxiety, we will evaluate several neurobehavioral models with respect to those characteristics. Parsing the strengths and weaknesses of these models as well as analyzing the mechanisms and circuitry that underlie fear learning may point toward a better understanding of the fear/anxiety distinction. It should also help forge a clearer relationship between these models and specific anxiety disorders. We also clarify the relationship of the RDoc criteria to these animal models.

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“…Classic lesion and stimulation studies combined with tract tracing have clearly mapped the landscape and identified critical neural hubs for expression of particular behaviours, but more often than not there are multiple behaviours regulated at an individual hub. For instance, the ventromedial nucleus of the hypothalamus is essential for expression of female sexual receptivity [54,55], but also modulates male mating and aggression [56]. In this issue, Bayless and Shah [44] emphasize the power of the mouse model to allow for targeted deletion or stimulation of specific sets of neurons, such as only those expressing the aromatase enzyme or the androgen receptor, and thereby disentangling the role of those specific neurons from their immediate but distinct neighbours.…”

Section: (B) Modular Control Of Behaviour Via Neural Circuitsmentioning

confidence: 99%

Multifaceted origins of sex differences in the brain

McCarthy

2016

Phil. Trans. R. Soc. B

146

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Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.

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Ventromedial hypothalamic neurons control a defensive emotion state

Cited by 968 publications

References 124 publications

The neural circuits of innate fear: detection, integration, action, and memorization

The neural circuits of innate fear: detection, integration, action, and memorization

Neurobehavioral perspectives on the distinction between fear and anxiety

Multifaceted origins of sex differences in the brain

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