The Neurological Ecology of Fear: Insights Neuroscientists and Ecologists Have to Offer one Another

“…by Sheriff et al. (2010), have been well-studied in relation to stress effects on maternal care in laboratory rodents, and have been shown to be associated with DNA methylation of genes affecting glucocorticoid receptor function in the hippocampus (Weaver et al., 2004; Kappeler and Meaney, 2010).”

“…levels of predator exposure, to test if maternal predator exposure affects DNA methylation in their offspring’s hippocampus in a manner similar to the way in which childhood abuse evidently affects DNA methylation in humans, as shown in the aforementioned suicide study (McGowan et al., 2008, 2009).”

“Independently, wildlife ecologists have begun to arrive at a similar conclusion, following a line of inquiry that began in the 1990s (Creel and Christianson, 2008).”

“Free-living animals can, and do, simply flee or avoid, a predator in a cage, predator models, or predator odor stations (e.g., Stankowich and Blumstein, 2005).”

“…and pharmacological agents known to affect symptoms in human patients should correct, with equal efficacy, comparable symptoms in the animal (Rosen and Schulkin, 1998; Roseboom et al., 2007; Stam, 2007; Armario et al., 2008; Masini et al., 2009; Mitra et al., 2009; Cohen et al., 2010).”

“…meter) outdoor enclosures may fulfill these requirements when studying very small animals (e.g., mice or songbirds), whereas housing an animal in a somewhat larger cage than usual in an animal care building (e.g., Blanchard and Blanchard, 1989; Choi and Kim, 2010) does not meet these criteria.”

“Behavioral (e.g., Kotler, 1992) and physiological (e.g., Boonstra et al., 1998) studies began, in the 1990s, to suggest that predatorinduced fear and stress could have lasting effects on animals in the wild, but because of the logistical challenges involved the critical experiments necessary to…”

“, Darwinian fitness), such as an effect on subsequent reproduction, must be maladaptive; and since the “function” of the stress axis is to maintain homeostasis, chronic stress must be pathological (Lupien et al., 2009; Rodrigues et al., 2009; Sheriff et al., 2009).”

“…or lasting effect on fitness (i.e., Darwinian fitness), such as an effect on subsequent reproduction, must be maladaptive; and since the “function” of the stress axis is to maintain homeostasis, chronic stress must be pathological (Lupien et al., 2009; Rodrigues et al., 2009; Sheriff et al., 2009).”

“Moreover, for organisms that rely more on sound and sight than smell, such as birds and humans, auditory stimuli are generally more meaningful than olfactory ones (Jarvis, 2004), and acoustic cues may frequently be more alarming than visual ones (Cohen et al., 2010).”

“…to PTSD. Epigenetic modifications involve longlasting, often environmentally induced, changes in gene expression and function, that can be inter-generationally transmissible (i.e., heritable), though the DNA sequence itself remains unchanged (Champagne and Curley, 2009; Yehuda and Bierer, 2009).”

“Eggers et al. (2006) reported effects of predator call playbacks on the number of eggs laid by Siberian jays, and Fontaine and Martin (2006) found that where predators were removed songbirds laid heavier eggs.”

“Calisi and Bentley (2009) recently proposed that studying neurobiology and behavior in semi-natural settings may provide a means to merge lab and field approaches.”

“Whereas a number of lab studies have mapped the expression of the immediate-early gene c-fos, in response to predator exposure (Dielenberg et al., 2001; Roseboom et al., 2007; Campeau et al., 2008), c-fos is rapidly expressed (within <1 h; Armario et al., 2008) and rapidly down-regulated (Staples…”

“However, though MRI is non-destructive it is necessarily invasive and may be very injurious depending upon the method used (e.g., the manganese used in manganese-enhanced MRI is potentially toxic; Silva et al., 2004).”

“…growing number of experimental and observational field studies show that predator-induced fear and stress has long-lasting effects on animals in the wild (Creel and Christianson, 2008; Hawlena and Schmitz, 2010), comparable to those documented by investigators addressing the predator model of PTSD.”

“…(2009) study did not allow them to determine whether these differences in dendritic morphology were pre-existing or induced by predator exposure, Mitra and Sapolsky (2008) reported changes in dendritic morphology in response to a single day of stress, suggesting that predator-induced fear…”

“Eggers et al. (2006) reported effects of predator call playbacks on the number of eggs laid by Siberian jays, and Fontaine and Martin (2006) found that where predators were removed songbirds laid heavier eggs.”

“…levels of predator exposure, to test if maternal predator exposure affects DNA methylation in their offspring’s hippocampus in a manner similar to the way in which childhood abuse evidently affects DNA methylation in humans, as shown in the aforementioned suicide study (McGowan et al., 2008, 2009).”

“We also thank two anonymous reviewers for their very helpful comments on an earlier draft. demonstrated lasting effects on glucocorticoid levels associated with variation in predator abundance (Clinchy et al., 2004, 2011), and the probability of suffering nest predation (Travers et al., 2010).”

“Predator exposure was initially seized upon for practical reasons as this permits the researcher to utilize a (1) psychological stressor, that is (2) life-threatening, but (3) does not involve pain; all consistent with the etiology of PTSD in humans (Adamec and Shallow, 1993; Roseboom et al., 2007; Campeau et al., 200…”

“Predator exposure in the lab results in changes in plasma glucocorticoid levels (Blanchard et al., 1998; Roseboom et al., 2007; Takahashi et al., 2008; Masini et al., 2009) and the same has been shown in both birds and mammals in the field (Hawlena and Schmitz, 2010).”

“…lasting effects stem from the unnatural conditions of captivity, i.e., it is not the fact of predator exposure but the fact the predator is inescapable that must explain these effects, since the animal cannot flee from the predator as it naturally would (Creel et al., 2009; Jöngren et al., 2010).”

“…increase vulnerability to developing subsequent long-term behavioral disruptions when exposed to a predator in adulthood (Cohen et al., 2006), consistent with the growing evidence that individual variation in susceptibility to PTSD is influenced by early-life experiences (Yehuda and Bierer, 2009).”

“To measure effects in conscious animals requires acclimation to being restrained in this manner, which takes several days in laboratory animals (King et al., 2005), and may be unachievable in many wild-caught animals.”

“Sheriff et al. (2010) reported that at a population level, predator exposure, mean maternal FCM levels, and mean juvenile FCM levels, were all correlated, suggesting that predator-induced glucocorticoid changes in mother hares affect their offspring’s glucocorticoid levels.”

“…and pharmacological agents known to affect symptoms in human patients should correct, with equal efficacy, comparable symptoms in the animal (Rosen and Schulkin, 1998; Roseboom et al., 2007; Stam, 2007; Armario et al., 2008; Masini et al., 2009; Mitra et al., 2009; Cohen et al., 2010).”

“(2007) euthanized rats 3 h after predator exposure, and found increased CRH-binding protein gene expression in the amygdala, consistent with previous studies (Schulkin et al., 2005).”

“, 2004, 2011), and the probability of suffering nest predation (Travers et al., 2010).”

“…of PTSD has been validated, in part, by the numerous studies showing that pharmacological agents known to affect symptoms of PTSD in human patients also correct comparable symptoms in animals exposed to predators (Cohen et al., 2006, 2010; Stam, 2007; Armario et al., 2008; Nanda et al., 2008).”

“…by Sheriff et al. (2010), have been well-studied in relation to stress effects on maternal care in laboratory rodents, and have been shown to be associated with DNA methylation of genes affecting glucocorticoid receptor function in the hippocampus (Weaver et al., 2004; Kappeler and Meaney, 2010).”

“…in DNA methylation ought to be detectable in the brains of animals in the wild collected under less than ideal field conditions, as recently corroborated by Pilsner et al. (2010) in a study that examined DNA methylation in the brains of polar bears shot by aboriginal hunters in eastern Greenland.”

“…linked to fear), as well as many other phenomena associated with PTSD (Adamec and Shallow, 1993; Schulkin et al., 2005; Roseboom et al., 2007; Stam, 2007; Armario et al., 2008; Campeau et al., 2008; Rosen et al., 2008; Takahashi et al., 2008; Masini et al., 2009; Mitra et al., 2009; Staples…”

“Predator exposure was initially seized upon for practical reasons as this permits the researcher to utilize a (1) psychological stressor, that is (2) life-threatening, but (3) does not involve pain; all consistent with the etiology of PTSD in humans (Adamec and Shallow, 1993; Roseboom et al., 2007; Campeau et al., 200…”

“Karels et al. (2000) similarly showed that where predators were removed the proportion of arctic ground squirrel females weaning young was increased.”

“MRI has also been used to assess neuroactivity in response to other stimuli in mice and songbirds (Van der Linden et al., 2007).”

“…to fear), as well as many other phenomena associated with PTSD (Adamec and Shallow, 1993; Schulkin et al., 2005; Roseboom et al., 2007; Stam, 2007; Armario et al., 2008; Campeau et al., 2008; Rosen et al., 2008; Takahashi et al., 2008; Masini et al., 2009; Mitra et al., 2009; Staples et al., 2009).”

“We also thank two anonymous reviewers for their very helpful comments on an earlier draft. demonstrated lasting effects on glucocorticoid levels associated with variation in predator abundance (Clinchy et al., 2004, 2011), and the probability of suffering nest predation (Travers et al., 2010).”

“…in attempting to understand PTSD, because long-lasting predator-induced fear and stress is ethologically and ecologically relevant, and represents a valid experience applicable to animals in their natural environment (Roseboom et al., 2007; Cantor, 2009; Staples et al., 2009; Cohen et al., 2010).”

“Predator exposure was initially seized upon for practical reasons as this permits the researcher to utilize a (1) psychological stressor, that is (2) life-threatening, but (3) does not involve pain; all consistent with the etiology of PTSD in humans (Adamec and Shallow, 1993; Roseboom et al., 2007; Campeau et al., 200…”

“…and pharmacological agents known to affect symptoms in human patients should correct, with equal efficacy, comparable symptoms in the animal (Rosen and Schulkin, 1998; Roseboom et al., 2007; Stam, 2007; Armario et al., 2008; Masini et al., 2009; Mitra et al., 2009; Cohen et al., 2010).”

“Behavioral (e.g., Kotler, 1992) and physiological (e.g., Boonstra et al., 1998) studies began, in the 1990s, to suggest that predatorinduced fear and stress could have lasting effects on animals in the wild, but because of the logistical challenges involved the critical experiments necessary to…”

“…in attempting to understand PTSD, because long-lasting predator-induced fear and stress is ethologically and ecologically relevant, and represents a valid experience applicable to animals in their natural environment (Roseboom et al., 2007; Cantor, 2009; Staples et al., 2009; Cohen et al., 2010).”

“The suitability of using predator exposure in exploring the animal model of PTSD has been validated, in part, by the numerous studies showing that pharmacological agents known to affect symptoms of PTSD in human patients also correct comparable symptoms in animals exposed to predators (Cohen et al., 2006, 2010; Stam,…”

“A number of recent neuroimaging studies using magnetic resonance imaging (MRI) have evaluated the neurological effects of exposure to predator odor in lab rats (e.g., Chen et al., 2007; Febo et al., 2009; Huang et al., 2011).”

“…in the lab that appear most readily translatable to the field, and detail the advantages that studying animals in the wild can offer researchers investigating the “predator model of PTSD.” Keywords: animal model of PTSD, indirect predator effects, post-traumatic stress disorder, predation…”

“Many researchers have adopted utilizing exposure to a predator (e.g., showing a rat a cat; Adamec and Shallow, 1993), or predator odor, as a stressor, in exploring the animal model of PTSD (Cohen et al., 2010; Mackenzie et al., 2010).”

“A number of recent neuroimaging studies using magnetic resonance imaging (MRI) have evaluated the neurological effects of exposure to predator odor in lab rats (e.g., Chen et al., 2007; Febo et al., 2009; Huang et al., 2011).”

“Predator exposure was initially seized upon for practical reasons as this permits the researcher to utilize a (1) psychological stressor, that is (2) life-threatening, but (3) does not involve pain; all consistent with the etiology of PTSD in humans (Adamec and Shallow, 1993; Roseboom et al., 2007; Campeau et al., 200…”

“A number of recent neuroimaging studies using magnetic resonance imaging (MRI) have evaluated the neurological effects of exposure to predator odor in lab rats (e.g., Chen et al., 2007; Febo et al., 2009; Huang et al., 2011).”

“Predator exposure early in life has also been shown to increase vulnerability to developing subsequent long-term behavioral disruptions when exposed to a predator in adulthood (Cohen et al., 2006), consistent with the growing evidence that individual variation in susceptibility to PTSD is…”

“Jöngren et al. (2010) euthanized chickens 2 week after predator exposure and identified 13 significantly differentially expressed genes in the midbrain.”

“…of PTSD has been validated, in part, by the numerous studies showing that pharmacological agents known to affect symptoms of PTSD in human patients also correct comparable symptoms in animals exposed to predators (Cohen et al., 2006, 2010; Stam, 2007; Armario et al., 2008; Nanda et al., 2008).”

“Clinchy et al. (2011a) recently reviewed various other neurological measures developed in laboratory animal studies of predatorinduced fear and stress that also ought to be adaptable to use in the field, given the less than ideal conditions that will typically apply when collecting samples from the…”

“We do not know whether animals in nature respond this way, but can conceive that a single predator attack in some species or a severe attack by a dominant conspecific may produce an animal that chronically anticipates more of the same and is thus chronically stressed (Clinchy et al. 2011).”

“…most reliable and readily inter-pretable means of testing the reactions of free-living wildlife to predator cues (Durant 2000; Eggers et al. 2006; Clinchy et al. 2011; Zanette et al. 2011; Hua et al. 2014; LaManna and Martin 2016; Suraci et al. 2016), and a 2014 review identified 180 such…”

“Indeed, field studies of animals in their natural habitat have shown that exposure to predators or associated cues lead to increased glucocorticoid levels, and decreased number of offspring (Clinchy et al., 2010).”

“…& King, 2008), reduce anxiety (Sheppard & Mills, 2003), create new models for human pathophysiology (Cohen et al., 2006; Mackenzie et al., 2010; Clinchy et al., 2011), and develop olfactory applications for military use Biological Reviews 93 (2018) 98–114 © 2017 Cambridge Philosophical…”

“Although there is debate as to whether naturally occurring chronic stress results in pathology (Boonstra, 2012), immunosuppression and illness are commonly linked to chronic intermittent stress (Cohen et al., 2007).”

“Previous studies have documented that a single traumatic event is sufficient to impact the neurological development of the mammalian brain [17,18,33,34], and the large hippocampus of the African elephant, which mediates social memory, is thought to be particularly susceptible during growth to adolescence [19].”

“Indeed, many experts have drawn parallels between PTSD and the adaptive response of animals to predation risk (e.g. Belzung & Lemoine, 2011; Clinchy et al., 2011; Goswami et al., 2013).”

“…additional explanatory power is o ff ered by connecting neural structure and function to an ecologically situated, embodied and embedded cognitive architecture selected for by evolutionary pressures (Bracha et al., 2004; Clinchy et al., 2011; Dodgson & Gordon, 2009; LeDoux, 2012; Roelofs, 2017).”

“Our approach that partners neuroscientists with ecologists could be used to better understand the neural bases of cognition in widely diverse animals (29).”

“Studies in wild animals existing in the context in which they have evolved will be particularly useful in understanding the ultimate causes of epigenetic plasticity (Clinchy et al., 2010; Love et al., 2012).”

“2008), with chronically elevated stress levels affecting metabolism, immune response, reproduction and/ or survival (Boonstra et al. 1998; Sapolsky, Romero & Munck 2000; Sheriff, Krebs & Boonstra 2009; Clinchy et al. 2011).”

“Capturing may cause an acute elevation in stress hormone output, but it might also alter the long term stress physiology of the animal (Boonstra, 2013; Clinchy et al., 2011) if a return to normal state is not achieved between capture events.”

“…a powerful, comparatively easily implemented and readily interpretable means of directly testing the behavioural responses of animals (Durant 2000a; Clinchy et al. 2011; Zanette et al. 2011; Suraci et al. 2016), and have accordingly been employed in hundreds of wildlife studies to quantify how…”

“Comparing time spent freezing during the TMT exposure and context re-exposure revealed a significant phenotype × time interaction [F(2,14)= 6.”

“Which of the behavioral stress responses seen in the laboratory appear in wild animals in the field? What is the meaning of the “traumatic” or “stressogenic” phonotype in nature? Is there such a thing? We suggest that both for researchers studying the predator model of PTSD and for ecologists, collaborative studies of…”

“Because glucocorticoids can be secreted in response to anthropogenic and natural perturbations (Sheriff et al. 2011) and emotions such as fear (Rodrigues et al. 2009; Clinchy et al. 2011), they are of particular interest in the study of stress and translocation.”

“Which of the behavioral stress responses seen in the laboratory appear in wild animals in the field? What is the meaning of the “traumatic” or “stressogenic” phenotype in nature? Is there such a thing?We suggest that both for researchers studying the predator model of PTSD and for ecologists, collaborative studies of…”

“Although cortisol is involved in numerous metabolic functions in both basal and stress-induced contexts, prolonged exposure to high levels of cortisol due to continued or repeated exposure to stressors may be deleterious (Bonier et al. 2009; Clinchy et al. 2011; Boonstra 2013).”

“(Oppenheim, 2019; Wolff, 2003) that includes studies of outbred populations with highly-variable genes (Modlinska and Pisula, 2020), and with multiple animals exposed to competing stimuli in semi-realistic or naturalistic settings (Clinchy et al., 2011).”

“One of the greatest research challenges of mechanisms involved in psychiatric disorders is the difficulty in replicating the symptoms of the disease in animal models [43], and it is important to develop new ethologically relevant models for translational research of psychiatric disorders [5,44].”

“This area of predator–prey research is often called the ‘ecology of fear’ due to the physiological stress and neuro-behavioural responses predators cause in prey (Preisser and Bolnick, 2008; Clinchy et al. 2011).”

“For example, chronically elevated predation risk has been shown to reduce reproduction (13, 14) and also negatively impact animal welfare via physiological (15, 16), nutritional (17, 18), behavioral (19, 20), and mental states (21, 22) of wild animals.”

“, 2012), and the mechanisms employed to mitigate its consequences (Clinchy et al., 2011; Fendt et al., 2020) are central to understanding anxieties in humans (Gorman, 2008; Kinsella and Monk, 2009), wildlife conservation and welfare (Berger, 2007; Gaynor et al.”

“This fear of predators can be overt and explicit, subtly changing our responses to these species (Clinchy et al., 2011; Prokop & Fančovičová, 2013; Mobbs et al., 2015; Nyhus, 2016).”

“Chronically elevated stress levels affect metabolism, immune response, reproduction and survival (Boonstra et al. 1998; Sapolsky et al. 2000; Sheriff et al. 2009; Clinchy et al. 2011).”

“…shown reduced feeding rate (Dudeck, Clinchy, Allen, & Zanette, 2018; Peluc et al., 2008), clutch size (Eggers et al., 2006; Zanette, White, Allen, & Clinchy, 2011), number of offspring and nest survival (Zanette et al., 2011), increased body mass (Walters et al., 2017) and have altered various…”

“In particular, it is not known if there are “ post-trauma ” symptoms for animals in the wild or which behavioral stress responses observed in the laboratory appear in wild animals in the fi eld [9, 15].”

“Behavior certainly mediates suppression and facilitation between mammalian carnivores because these interactions take place between cognitive species (Clinchy et al. 2011).”

“……………………………………….31 2.7.3 Glutamate uncaging experiments……………………………………..32 Chapter III: Properties of extinction in resilient and PTSD-like rats…...…...33 3.1 Rationale…………………..............................................................................34 3.2 Hypothesis…………………………………………………………………………35 3.3 Methods………………………”

“Pre-dation risk can alter reproduction and behaviour and have lasting physiological consequences (e.g., effects on repro - duction, Clinchy et al. 2011 ; effects on decision-making and reproduction, Lima, 1998).”