How much fear is in anxiety?

Genewsky, Andreas; Albrecht, Nettie N.; Sa, Bura; Pm, Kaplick; Heinz, D. E.; Nussbaumer, Markus; Engel, Mareen; Grünecker, Barbara; Sf, Kaltwasser; Cj, Riebe; Bt, Bedenk; Czisch, Michael; Wotjak, CT

doi:10.1101/385823

Cited by 5 publications

(5 citation statements)

References 126 publications

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“…We found that a dose of diazepam that was anxiolytic in wildtype mice had no effect in C3aR -/mice. Stretch attend postures, thought to reflect risk assessment behaviour 54 , are highly sensitive to pharmacological manipulation 50,80 and in agreement with our own findings, diazepam has been shown to specifically decrease SAPs in the absence of effects on open arm exploration 81 . Importantly, C3aR -/mice consistently performed more SAPs than other genotypes, and therefore floor effects cannot account for the pattern of results observed.…”

Section: Discussionsupporting

confidence: 87%

Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder

Westacott

Humby

Haan

et al. 2022

Brain, Behavior, and Immunity

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Complement is a key component of the immune system with roles in inflammation and host-defence. Here we reveal novel functions of complement pathways impacting on emotional reactivity of potential relevance to the emerging links between complement and risk for psychiatric disorder. We used mouse models to assess the effects of manipulating components of the complement system on emotionality. Mice lacking the complement C3a Receptor (C3aR -/-) demonstrated a selective increase in unconditioned (innate) anxiety whilst mice deficient in the central complement component C3 (C3 -/-) showed a selective increase in conditioned (learned) fear. The dissociable behavioural phenotypes were linked to different signalling mechanisms.Effects on innate anxiety were independent of C3a, the canonical ligand for C3aR, consistent with the existence of an alternative ligand mediating innate anxiety, whereas effects on learned fear were due to loss of iC3b/CR3 signalling. Our findings show that specific elements of the complement system and associated signalling pathways contribute differentially to heightened states of anxiety and fear commonly seen in psychopathology.

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Section: Discussionsupporting

confidence: 87%

Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder

Westacott

Humby

Haan

et al. 2022

Brain, Behavior, and Immunity

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show abstract

Section: Discussionsupporting

confidence: 87%

“…, are highly sensitive to pharmacological manipulation40,72 and in agreement with our own findings, diazepam has been shown to specifically decrease SAPs in the absence of effects on open arm exploration73 . Importantly, C3aR -/mice consistently performed more SAPs than other genotypes, and therefore floor effects cannot account for the pattern of results observed.…”

supporting

confidence: 89%

Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder

Westacott

Humby

Haan

et al. 2019

Preprint

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length: 244/250 Abstract 33 Background Recent findings implicate complement, a key component of the 34 immune system, in healthy brain functioning and risk for psychiatric disorders. 35Altered emotional function, in particular maladaptive fear and anxiety, is a pervasive 36 and clinically important symptom across several neuropsychiatric disorders. In this 37 work we examined the extent to which different complement pathways impact on 38 dissociable components of anxiety and learned fear. 39 Methods: C3 -/and C3aR -/mice were assessed in a battery of tests assaying innate 40 anxiety and learned fear. The effects of systemic diazepam (2mg/kg) and the C3aR 41 antagonist SB290157 (10mg/kg) on behaviour was assessed. Expression of genes 42 linked to anxiety, stress responses and risk for psychiatric disorder were assessed in 43 brain regions implicated in fear and anxiety. 44 Results: The data indicated a robust and highly reproducible double-dissociation of 45 C3 and C3aR on learned fear and innate anxiety, respectively. We probed 46 downstream complement pathways responsible for the C3-specific effects on 47 Conclusions: These findings reveal novel functions and unexpected dissociations 55between the C3 and C3aR pathways impacting on specific emotional behaviours 56 relevant to psychiatric disorder.

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“…36 Many studies based their conclusions on these lines, yet recent work revealed that the mice considered as exhibiting low anxiety actually suffer from full retinal blindness, which could explain their seemingly fearless demeanor in the maze. 37 We have recently demonstrated a computational approach to measuring personality, starting from groups of mice. 38 Personality is defined as being consistent and stable across time and contexts while varying among individuals.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Animal behavior and animal personality from a non-human perspective: Getting help from the machine

Forkosh

2021

Patterns

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We can now track the position of every fly's leg or immerse a tiny fish inside a virtual world by monitoring its gaze in real time. Yet capturing animals' posture or gaze is not like understanding their behavior. Instead, behaviors are still often interpreted by human observers in an anthropomorphic manner. Even newer tools that automatically classify behaviors rely on human observers for the choice of behaviors. In this perspective, we suggest a roadmap toward a "human-free" interpretation of behavior. We present several recent advances, including our recent work on animal personalities. Personality both underlies behavioral differences among individuals and is consistent over time. A mathematical formulation of this idea has allowed us to measure mouse traits objectively, map behaviors across species (humans included), and explore the biological basis of behavior. Our goal is to enable ''machine translation'' of raw movement data into intelligible human concepts en route to improving our understanding of animals and people.

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How much fear is in anxiety?

Cited by 5 publications

References 126 publications

Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder

Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder

Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder

Animal behavior and animal personality from a non-human perspective: Getting help from the machine

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