Freeze for action: neurobiological mechanisms in animal and human freezing

Upon increasing levels of threat, animals activate qualitatively different defensive modes, including freezing and active fight-or-flight reactions. Whereas freezing is a form of behavioural inhibition accompanied by parasympathetically dominated heart rate deceleration, fight-or-flight reactions are associated with sympathetically driven heart rate acceleration. Despite the potential relevance of freezing for human stress-coping, its phenomenology and neurobiological underpinnings remain largely unexplored in humans. Studies in rodents have shown that freezing depends on amygdala projections to the brainstem (periaqueductal grey). Recent neuroimaging studies in humans have indicated that similar brain regions may be involved in human freezing. In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections. This review paper presents a model detailing these neural mechanisms involved in freezing and the shift to fight-or-flight action. Freezing is not a passive state but rather a parasympathetic brake on the motor system, relevant to perception and action preparation. Study of these defensive responses in humans may advance insights into human stress-related psychopathologies characterized by rigidity in behavioural stress reactions. The paper therefore concludes with a research agenda to stimulate translational animal–human research in this emerging field of human defensive stress responses. This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.

Download Full-text

Loss of mGluR5 in D1 Receptor-Expressing Neurons Improves Stress Coping

International Journal of Molecular Sciences ◽

10.3390/ijms22157826 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7826

Author(s):

Luca Zangrandi ◽

Claudia Schmuckermair ◽

Hussein Ghareh ◽

Federico Castaldi ◽

Regine Heilbronn ◽

...

Keyword(s):

Stress Responses ◽

Metabotropic Glutamate Receptor ◽

Forced Swim Test ◽

Functional Integration ◽

D1 Receptor ◽

Conditional Knockout ◽

Stress Coping ◽

Metabotropic Glutamate ◽

Internal States

The metabotropic glutamate receptor type 5 (mGluR5) has been proposed to play a crucial role in the selection and regulation of cognitive, affective, and emotional behaviors. However, the mechanisms by which these receptors mediate these effects remain largely unexplored. Here, we studied the role of mGluR5 located in D1 receptor-expressing (D1) neurons in the manifestation of different behavioral expressions. Mice with conditional knockout (cKO) of mGluR5 in D1 neurons (mGluR5D1 cKO) and littermate controls displayed similar phenotypical profiles in relation to memory expression, anxiety, and social behaviors. However, mGluR5D1 cKO mice presented different coping mechanisms in response to acute escapable or inescapable stress. mGluR5D1 cKO mice adopted an enhanced active stress coping strategy upon exposure to escapable stress in the two-way active avoidance (TWA) task and a greater passive strategy upon exposure to inescapable stress in the forced swim test (FST). In summary, this work provides evidence for a functional integration of the dopaminergic and glutamatergic system to mediate control over internal states upon stress exposure and directly implicates D1 neurons and mGluR5 as crucial mediators of behavioral stress responses.

Download Full-text

Heart-rate deceleration predicting the determination of costly punishment: Implications for its involvement in cognitive effort expended in overriding self-interest

International Journal of Psychophysiology ◽

10.1016/j.ijpsycho.2016.09.017 ◽

2016 ◽

Vol 109 ◽

pp. 29-36 ◽

Cited By ~ 1

Author(s):

Takahiro Osumi ◽

Hideki Ohira

Keyword(s):

Heart Rate ◽

Cognitive Effort ◽

Heart Rate Deceleration ◽

Costly Punishment ◽

Self Interest ◽

Rate Deceleration

Download Full-text

Responses to social evaluative stress in regular cannabis smokers

Journal of Psychopharmacology ◽

10.1177/0269881120972337 ◽

2021 ◽

pp. 026988112097233

Author(s):

Richard J Xia ◽

Thomas Chao ◽

Divya Patel ◽

Gillinder Bedi

Keyword(s):

Heart Rate ◽

Stress Responses ◽

Social Stress ◽

Physiological Stress ◽

Negative Mood ◽

Mood States ◽

Residual Effects ◽

Subjective Response ◽

Negative Mood States ◽

Stress Responding

Background: Aspects of the canonical stress response differ in stimulant, opioid, and alcohol users relative to controls, and dysregulated responses to stress may contribute to continued use of these drugs. Little prior research has focused on stress responses in regular cannabis smokers. We assessed responses to a standardized laboratory social stress assay (the Trier Social Stress Task; TSST) in regular cannabis smokers (CANs) compared with controls (CONs). Methods: Healthy, non-treatment-seeking adult CANs (⩾4×/week; smoking cannabis as usual) and demographically matched CONs completed the TSST. Outcome measures were subjective mood, heart rate, and salivary cortisol. Results: Nineteen CANs (1 female) and 20 CONs (2 female) participated; groups were matched on trauma exposure, sex, race, and age. CANs smoked cannabis 6.4 ± 1.1 days/week. Eight CANs and one CON smoked tobacco cigarettes daily. Overall, the TSST produced expected increases in anxiety, negative mood states, cortisol, and heart rate. CANs had blunted subjective response to stress relative to CONs, but they did not differ in physiological (cortisol and cardiovascular) stress responding. Conclusion: These results indicate that CANs have blunted mood responses to social stress, but normative physiological stress responding. Observed differences could be due to residual effects of cannabis, reluctance to endorse negative mood states, or to issues related to identifying (i.e., emotional identification) or feeling (i.e., interoception) stress-related affective states. Further research is warranted to characterize the mechanisms of these differences and assess implications for daily functioning and treatment outcomes.

Download Full-text

Npas4a expression in the teleost forebrain is associated with stress coping style differences in fear learning

Scientific Reports ◽

10.1038/s41598-021-91495-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Matthew R. Baker ◽

Ryan Y. Wong

Keyword(s):

Neural Plasticity ◽

Coping Style ◽

Molecular Mechanisms ◽

Conditioned Fear ◽

Coping Styles ◽

Brain Regions ◽

Contextual Fear Conditioning ◽

Fear Learning ◽

Stress Coping ◽

Contextual Fear

AbstractLearning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive–reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4a and gabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly higher npas4a expression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the expression of activity-dependent genes like npas4a may be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.

Download Full-text

Heart rate responses and plasma cortisol concentrations in ewes: comparison between cervical and laparoscopic intrauterine insemination and their associated handling procedures

Animal Science ◽

10.1017/s1357729800009516 ◽

1998 ◽

Vol 66 (2) ◽

pp. 383-387 ◽

Cited By ~ 1

Author(s):

M. Khalid ◽

W. Haresign ◽

D. G. Bradley

Keyword(s):

Heart Rate ◽

Stress Responses ◽

Plasma Cortisol ◽

Intrauterine Insemination ◽

Management Practice ◽

Treatment Groups ◽

Cortisol Responses ◽

The Mean ◽

Pre Treatment ◽

Mean Heart Rate

AbstractThis study consisted of two experiments. In experiment 1, stress responses of sheep which were restrained either in a laparoscopy cradle or a roll-over cradle were compared. The results of this experiment indicated that restraint in roll-over cradle is less (P < 0·05) stressful than that in a laparoscopy cradle when assessed in terms of the elevation and duration of both the mean heart rate and plasma cortisol responses. Experiment 2 compared the stress responses of sheep subjected to restraint in a laparoscopy cradle, restraint in a laparoscopy cradle with intrauterine artificial insemination (AI) by laparoscopy, minimal restraint with cervical AI or restraint in a roll-over cradle plus foot-trimming. All treatments resulted in significant elevations in both heart rate and plasma cortisol concentrations (F < 0·001). The peak heart rate was significantly (P < 0·05) higher in ewes subjected to cervical AI than in those subjected to intrauterine insemination, with other treatments intermediate. The peak cortisol response did not differ among different treatments. The duration over which both the mean heart rate and -plasma cortisol concentrations remained significantly elevated above pre-treatment concentrations did not differ among treatment groups. The results of this study suggest that while restraint using a laparoscopy cradle is more stressful than that using a rollover cradle, the stress inflicted by intrauterine insemination by laparoscopy itself is no greater than that due to restraint using the laparoscopy cradle alone, cervical AI or the management practice offoot-trimming using a rollover cradle.

Download Full-text

Anticipatory Heart Rate Deceleration and Reaction Time in Children with and without Referral for Learning Disability

Child Development ◽

10.2307/1128046 ◽

1973 ◽

Vol 44 (2) ◽

pp. 267 ◽

Cited By ~ 61

Author(s):

L. Alan Sroufe ◽

Barbara C. Sonies ◽

Winifred D. West ◽

Francis S. Wright

Keyword(s):

Heart Rate ◽

Reaction Time ◽

Learning Disability ◽

Heart Rate Deceleration ◽

Rate Deceleration

Download Full-text

The mitochondrial uniporter controls fight or flight heart rate increases

Nature Communications ◽

10.1038/ncomms7081 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 87

Author(s):

Yuejin Wu ◽

Tyler P. Rasmussen ◽

Olha M Koval ◽

Mei-ling A. Joiner ◽

Duane D. Hall ◽

...

Keyword(s):

Heart Rate ◽

Fight Or Flight

Download Full-text

Fight or Flight: The Effect of Heart Rate Reactivity on Acute Stress-Induced Food Intake

Physiology & Behavior ◽

10.1016/j.physbeh.2022.113704 ◽

2022 ◽

pp. 113704

Author(s):

Benedict Herhaus ◽

Christina Bastianon ◽

Shiwa Ghassabei ◽

Katja Petrowski

Keyword(s):

Heart Rate ◽

Food Intake ◽

Acute Stress ◽

Heart Rate Reactivity ◽

Fight Or Flight

Download Full-text

Insights into the molecular basis of host behaviour manipulation by Toxoplasma gondii infection

Emerging Topics in Life Sciences ◽

10.1042/etls20170108 ◽

2017 ◽

Vol 1 (6) ◽

pp. 563-572 ◽

Cited By ~ 1

Author(s):

Pierre-Mehdi Hammoudi ◽

Dominique Soldati-Favre

Keyword(s):

Toxoplasma Gondii ◽

Stress Responses ◽

Molecular Mechanisms ◽

Brain Regions ◽

Intermediate Hosts ◽

Toxoplasma Gondii Infection ◽

Host Parasite ◽

Host Behaviour ◽

The Brain ◽

Brain Homeostasis

Typically illustrating the ‘manipulation hypothesis’, Toxoplasma gondii is widely known to trigger sustainable behavioural changes during chronic infection of intermediate hosts to enhance transmission to its feline definitive hosts, ensuring survival and dissemination. During the chronic stage of infection in rodents, a variety of neurological dysfunctions have been unravelled and correlated with the loss of cat fear, among other phenotypic impacts. However, the underlying neurological alteration(s) driving these behavioural modifications is only partially understood, which makes it difficult to draw more than a correlation between T. gondii infection and changes in brain homeostasis. Moreover, it is barely known which among the brain regions governing fear and stress responses are preferentially affected during T. gondii infection. Studies aiming at an in-depth dissection of underlying molecular mechanisms occurring at the host and parasite levels will be discussed in this review. Addressing this reminiscent topic in the light of recent technical progress and new discoveries regarding fear response, olfaction and neuromodulator mechanisms could contribute to a better understanding of this complex host–parasite interaction.

Download Full-text