Knowing that an animal is fearful is crucial for many psychology and neuroscience studies. For instance, this knowledge allows researchers to examine the brain pathways involved in processing and responding to fear.

Typically, researchers consider that a rodent is experiencing fear if it ‘freezes’ – a response which, in the wild, helps to evade detection by predators. In Pavlovian fear conditioning experiments, for example, rats and mice freeze when exposed to a stimulus (often a specific sound) previously associated with unpleasant sensations. However, rodents can also respond more actively to threats, for instance by running or jumping away. It remains unclear whether the ‘fearful stimuli’ used in Pavlovian approaches specifically elicits only freezing, or other fear-related behaviors as well.

To investigate this, Chu et al. used high-speed cameras to record rats’ responses to a sound cue they had ‘learned’ to associate with a mild foot shock. In addition to freezing, the animals ran, jumped, stood on their hind legs and stopped their usual reward-seeking behavior in response to the cue. Crucially, these reactions were absent when the rats were exposed to sound cues not associated with pain.

Overall, these experiments demonstrate that Pavlovian conditioning can elicit a full range of fear-related behaviors beyond freezing. Understanding the neural activity behind these diverse responses could lead to more targeted therapies and interventions addressing the various ways stress and anxiety manifest in people.

Animals evolved defensive systems to detect and avoid predation. The predatory imminence continuum (PIC), a prominent theory of defensive behavior, identifies three defensive modes based on the proximity to predation: pre-encounter (leaving the safety of the nest), post-encounter (predator detected), and circa-strike (predation imminent or occurring) (Fanselow and Lester, 1988). Pavlovian fear conditioning has been extensively used to reveal the behavioral and neural underpinnings of defensive systems in rats (Bolles and Collier, 1976; Fanselow, 1993; Killcross et al., 1997; McNally et al., 2011). In a typical Pavlovian fear conditioning procedure, a rat is placed in a neutral context, and played an auditory cue whose termination coincides with foot shock delivery. Each PIC mode is characterized by a unique set of behaviors and, critically, each mode is thought to be captured by a unique epoch of a Pavlovian fear conditioning trial (Fanselow et al., 2019). The post-encounter mode is characterized by freezing, and is captured by cue presentation. Circa-strike is characterized by locomotion, jumping, and rearing, and is captured by shock delivery.

Freezing to a fear conditioned cue may be the most ubiquitous finding in all of behavioral neuroscience (Blanchard and Blanchard, 1969; Bolles and Collier, 1976; Maren et al., 1997; Anagnostaras, 1999; Wilensky et al., 1999; Quirk, 2002; Koo et al., 2004; Rogers and Kesner, 2004; Iordanova et al., 2006; Shumake et al., 2014; Foilb et al., 2016; Furlong et al., 2016). The relationship between freezing and Pavlovian fear conditioning is so strong that failing to observe freezing in defensive settings has been used to support assertions that Pavlovian fear conditioning did not occur (Zambetti et al., 2021). Cued fear as freezing has been further entrenched by historical observations that locomotion, jumping, and rearing (theorized circa-strike behaviors) are not elicited by fear conditioned cues (Fanselow et al., 2019). Instead, activity-promoting defensive behaviors are restricted to shock delivery (Fanselow, 1982) or to other sudden changes in stimuli (Fadok et al., 2017; Totty et al., 2021). Yet, locomotion, jumping, and rearing all readily occur in defensive settings (Blanchard et al., 1986; Holland, 1979; Dielenberg and McGregor, 2001). Most relevant, a fear conditioned cue can elicit locomotion, rapid forward movements termed ‘darting’ (Gruene et al., 2015; Mitchell et al., 2022).

The ability of a fear conditioned cue to elicit locomotion has been called into question (Trott et al., 2022). Trott et al. noted that in prior studies locomotion was greatest at cue onset – the time point most distal from shock delivery (Gruene et al., 2015; Fadok et al., 2017). Moreover, prior studies did not use associative controls (but see Totty et al., 2021) – essential to making claims that cue-elicited behaviors were due to a predictive relationship with foot shock. Using between-subjects designs in mice, Trott et al. ascribe the majority of cue-elicited locomotion to non-associative cue properties. The foundational study demonstrating the need for proper associative controls in any form of conditioning used Pavlovian fear conditioning (Rescorla, 1967). Not just all-or-none, the magnitude of a fear conditioned, cue-elicited response can scale with foot shock probability (Rescorla, 1968; Ray et al., 2020). Rescorla, 1968 many foundational associative learning studies (Kamin, 1969; Rescorla and Wagner, 1972), relied on experiments that did not measure ‘fear’ with freezing, but with suppression of operant responding for reward (now termed conditioned suppression) (Estes and Skinner, 1941). Drawing from Rescorla, 1968, our laboratory has devised a robust, within-subjects Pavlovian fear conditioning procedure in which three cues predict unique foot shock probabilities: danger (p = 1), uncertainty (p = 0.25), and safety (p = 0). Measuring conditioned suppression, we consistently observe complete behavioral discrimination: danger elicits greater suppression than safety, and uncertainty elicits suppression intermediate to danger and safety (Wright et al., 2015; DiLeo et al., 2016; Walker et al., 2018; Ray et al., 2022).

The goal of Experiment 1 was to construct comprehensive, temporal ethograms of rat behavior during discriminative Pavlovian fear conditioning, consisting of a danger, uncertainty, and safety cue. This would allow us to determine what behaviors come under the control of a fear conditioned cue, and how these behaviors are temporally organized. We had the ability to reveal freezing as the exclusive conditioned behavior, as prior studies have found positive relationships between conditioned freezing and conditioned suppression (Bouton and Bolles, 1980; Mast et al., 1982). Yet, we also had the ability to detect additional behaviors, as brain manipulations that impair conditioned freezing can have little or no impact on conditioned suppression (McDannald, 2010; McDannald and Galarce, 2011). A subgoal was to compare behaviors elicited by the deterministic danger cue, and the probabilistic uncertainty cue. The goal of Experiment 2 was to reveal which of these danger-elicited behaviors transferred to an extinction context in which shock and reward were not present. For Experiment 2, we simplified the discrimination procedure to include only the danger and safety cues.

Twenty-four rats (12 females; Experiment 1) and sixteen rats (8 females, Experiment 2) received Pavlovian fear discrimination. TTL-triggered GigE cameras were installed in behavioral boxes and programmed to capture frames at subsecond temporal resolution prior to and during cue presentation. 86,400 frames (Experiment 1) and 25,600 frames (Experiment 2) were hand scored for nine discrete behaviors reflecting reward (Holland, 1977), activity-suppressing fear (Blanchard and Blanchard, 1969; Fanselow, 1982), and activity-promoting fear (Blanchard et al., 1986; Dielenberg and McGregor, 2001; Gruene et al., 2015). Complete temporal ethograms were constructed during early, middle, and late conditioning sessions (Experiment 1), and for the two types of extinction tests (Experiment 2). Danger responding was compared to baseline and to safety, which served as an unpaired control cue. Behaviors elicited by the danger cue were considered associative (due to pairing with foot shock) if they differed both from baseline and from the safety cue. The temporal profile of responding was determined by tracking behavior change over cue presentation.

We set out to quantify behaviors elicited by a fear conditioned, danger cue. Consistent with virtually all studies of Pavlovian fear conditioning (but see Amorapanth et al., 1999), we observed danger-elicited freezing over the course of acquisition (Experiment 1) and during extinction testing (Experiment 2). Yet, freezing was not the dominant danger-elicited behavior. Instead, danger orchestrated a suite of behaviors. During Experiment 1, danger suppressed reward behavior directed toward the site of food delivery and the location of the rewarded action. Even more, danger-elicited locomotion, jumping, and rearing. During Experiment 2, danger again suppressed rewarded action and continued to elicit locomotion. During both experiments, freezing was most prominent at danger cue onset. Locomotion was most prominent toward danger cue offset (Experiment 1), and when shock would have occurred in extinction (Experiment 2).

Before discussing our results further, an important limitation should be raised. 40–50% of frames could not be assigned to a specific behavior and were labeled as background. This was due to three main factors. First, in order to objectively hand score many behaviors, we developed mutually exclusive, specific definitions. Our strict definitions meant erring on the side of labeling a behavior background if there was uncertainty in judgment. Second, use of a single, side view camera meant the observer could not view a rat’s forelimbs or face when the rat was turned away from the camera. If forelimb and face position could not be determined the frame was labeled background. Finally, transition behaviors (e.g., switching from rearing to locomotion) and other behaviors (e.g., sniffing and turning) that did not fit into one of the nine behavior definitions were labeled background. The upside of this limitation is high confidence in behavior judgments and high inter-rater reliability for those judgments.

Studies assessing auditory fear conditioning in a neutral context routinely report freezing to account for >80% of behavior during cue presentation (Bolles and Collier, 1976; Maren et al., 1997; Anagnostaras, 1999; Wilensky et al., 1999; Quirk, 2002; Koo et al., 2004; Rogers and Kesner, 2004; Iordanova et al., 2006; Shumake et al., 2014; Foilb et al., 2016; Furlong et al., 2016). The sheer number of demonstrations, and number of groups independently observing dominant freezing, puts us firmly in the minority. Placing us further in the minority, we observe danger-elicited locomotion, jumping, and rearing. These behaviors are characterized by lateral and vertical movements, polar opposites to the immobility that characterizes freezing. A commonality of the studies above was use of contexts in which only cues and shocks were delivered, with shocks being more intense than shocks used in our studies. These experimental settings favor freezing. It is likely that our inclusion of competing, reward behaviors and use of lower shock intensities permitted a broader range of danger-elicited behaviors to be observed (Holland, 1979; Mitchell et al., 2022).

Indeed, we are not the first group to observe locomotion, jumping, or rearing in defensive settings in rats. Using more traditional Pavlovian fear conditioning designs, Shansky and colleagues have observed ‘darting’, rapid forward movements across the test chamber, to a fear conditioned cue (Gruene et al., 2015). While more readily observed in female rats, darting can be observed in males under certain experimental conditions (Mitchell et al., 2022). Our definition of locomotion aligns well with the Shansky lab definition of darting. We found that danger-elicited locomotion was equally apparent during extinction, and more robust than freezing. While locomotion was observed across all rats, female locomotion was better timed to shock delivery. Our results join previous studies in demonstrating a fear conditioned cue promotes movement in rats (Bolles and Collier, 1976; Totty et al., 2021).

Jumping is elicited in rats by hypoxia (decreasing oxygen levels in the air) – a life-threatening condition (Spiacci et al., 2015). More relevant to our study, the Blanchards observed jumping in defensive settings in rats (Blanchard et al., 1986). In their procedure, a rat was placed at the end of an inescapable hallway, then a human experimenter slowly approached. Rats initially froze when the experimenter was distant (1–2 m away), but switched from freezing to jumping as the experimenter drew near (<1 m). Our observation of danger-elicited jumping during fear acquisition, and its preferential expression at the end of danger presentation, mirrored the defensive jumping pattern observed in the Blanchard’s study.

Rearing (Lever et al., 2006) is elicited by visual cues predicting moderate foot shock. Holland, 1979 found that a mix of rearing and freezing are acquired to a visual cue paired with low intensity foot shock. A visual cue paired with intense foot shock exclusively produces freezing. The foot shock intensity we used in both experiments (0.5 mA) is more consistent with the low intensities in the Holland, 1979 experiment. Dielenberg and McGregor, 2001 found that rats exposed to a recently worn cat collar, with an opposing box to hide in, show ‘vigilant rearing’ to the cat collar (Dielenberg and McGregor, 2001). Rearing was never observed in a control condition. While we cannot claim vigilance, we find that danger promotes rearing during fear acquisition.

Temporal ethograms revealed that during fear acquisition, jumping and rearing were most prevalent at the end of cue presentation – when foot shock was imminent. This was in contrast to freezing which was prominent during early danger presentation for both females and males, but only shown by males at the end of cue presentation. Though unlike Experiment 1, in which foot shock was present, we found no evidence of danger-elicited jumping and rearing during fear extinction. Because jumping and rearing are vertical behaviors, they may be avoidant or escape responses. The rat is trying to leave the floor before the shock comes on. This interpretation is supported by the finding that these responses peaked just before shock presentation in Experiment 1. Removing foot shock in Experiment 2 may have removed the impetus for avoidance and escape. However, it could be equally likely that these behaviors are more sensitive context change. Experiment 2 also found that freezing transferred less well to the extinction context in which reward was absent.

Our findings accord well with the PIC theory of defensive behavior (Fanselow and Lester, 1988). PIC theory identifies three defensive modes: pre-encounter (e.g., leaving the safety of the nest to forage), post-encounter (predator detected), and circa-strike (predation inevitable or occurring). Analogs to PIC modes are identified in a Pavlovian fear conditioning trial (Fanselow et al., 2019). Pre-encounter mode may correspond to leaving the home cage and being placed in the experimental chamber where foot shocks occur. Post-encounter mode corresponds to presentation of the fear conditioned cue. Circa-strike mode is said to correspond to foot shock delivery. It is argued that circa-strike behaviors (locomotion, jumping, and rearing) are not observed toward the end of danger presentation because rats do not time shock delivery. In support, extending cue duration in traditional cued fear conditioning paradigms does not result in shifts from freezing to locomotion, jumping, and rearing toward cue offset (Fanselow et al., 2019).

Here, we find expected patterns of defensive behavior in unexpected epochs of Pavlovian conditioning trials. Early danger freezing by all rats (females and males) gives way to a late mix of danger-elicited behaviors that included locomotion, jumping, and rearing (Experiment 1) or late locomotion (Experiment 2). Why do we observe late danger control of circa-strike behaviors? Hunger and the availability of a rewarded action may provide an impetus for shock timing. Timing would allow rats to minimize the display of defensive behaviors and maximize reward seeking. In support, presenting long duration danger cues in a conditioned suppression setting results in timing of fear responding. With experience, rats show little suppression of reward seeking to danger onset, which ramps toward shock delivery (Rosas and Alonso, 1996). Supporting the minimization of defensive behavior in reward settings, foot shocks signaled by danger will strongly suppress reward seeking only early in fear conditioning. Shock-induced suppression quickly wanes and with experience, shock delivery will paradoxically facilitate reward seeking (LaBarbera and Caul, 1976; Strickland et al., 2021). Shock timing information is readily apparent in the ventrolateral periaqueductal gray, a brain region central to defensive behavior (Fanselow, 1993; Carrive et al., 1997; Mobbs et al., 2007; McDannald, 2010; Tovote et al., 2016; Arico et al., 2017). Populations of ventrolateral periaqueductal gray neurons show little responding upon danger presentation, but ramp firing toward shock delivery (Ozawa et al., 2017; Wright and McDannald, 2019; Wright et al., 2019). Our results support the PIC theory of defensive behavior but demonstrate that the relationship between defensive mode and Pavlovian conditioning trial epoch is not fixed, but depends on the experimental setting.

A secondary goal of Experiment 1 was to compare defensive behaviors elicited by a deterministic, danger cue and a probabilistic, uncertainty cue. In our setting, uncertainty is not simply a diminished version of danger. Indeed, uncertainty only promoted a subset of danger-elicited behaviors: locomotion and jumping. Most surprising was the inability of uncertainty to suppress reward behaviors directed toward the food cup and port. This is particularly puzzling because using suppression ratios, we found uncertainty to produce robust suppression of nose poking. What is going on here? Food cup, port, and poke behavior lie on a rewarded action continuum. Food cup means the rat is in the area of food delivery – but is most distal from the rewarded action. Port means the rat is around or in the site of the rewarded action, but only poke requires the rat to be fully engaged in performing the rewarded action (nose all the way into the port). Danger suppresses all reward behavior regardless of proximity to rewarded action. In contrast, uncertainty selectively suppresses reward behavior most proximal to the rewarded action.

By comprehensively quantifying behavior and constructing temporal ethograms, we found a fear conditioned cue to independently control at least six distinct behaviors during fear acquisition and three distinct behaviors during fear extinction. Though our study was exclusively behavioral, we feel our results have implications for investigations into the neural basis of fear learning and the organization of defensive behavior. Most important is that a fear conditioned cue does not simply elicit freezing. Behaviors elicited by a fear conditioned cue are the product of many factors: species, sex, age, behavioral setting, and experimenter-determined parameters (CS/US type, duration, and intensity; trial number, inter-trial interval [ITI], and more). In our view, freezing is a common – not dominant – defensive behavior because the field has favored behavioral settings and experimenter-determined parameters that maximize the expression of ‘fear’ through freezing (McDannald, 2023). Here, we show that a relatively simple modification of the rat’s behavioral setting – access to a rewarded action – is sufficient to de-emphasize freezing and promote the expression of many additional behaviors. Most prominent of these is locomotion. Even more, Pavlovian fear conditioning over a baseline of reward seeking reveals a temporally organized sequence of cue-elicited defensive behaviors predicted by PIC theory. The independent expression of these behaviors is appealing for studies attempting to link discrete behavioral sequelae of ‘fear’ to distinct neural circuits, breathing new life into a classic Pavlovian fear conditioning procedure (Estes and Skinner, 1941).

All procedures were performed in the Boston College Animal Care Facility in accordance with NIH and Boston College guidelines. The Boston College experimental protocol supporting these procedures is 2024-001.

Raw images and observer judgments are freely available: https://doi.org/10.7910/DVN/HKMUUN.

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Author details

1. Amanda Chu

   Department of Psychology and Neuroscience, Boston College, Chestnut Hill, United States

   Contribution

   Conceptualization, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, Visualization, Methodology, Writing – original draft, Project administration, Writing – review and editing

   For correspondence

   amanda.chu@bc.edu

   Competing interests

   No competing interests declared

   Additional information

   Lead contacts

   "This ORCID iD identifies the author of this article:" 0000-0002-5590-3245

2. Nicholas T Gordon

   Department of Psychology and Neuroscience, Boston College, Chestnut Hill, United States

   Contribution

   Data curation, Formal analysis

   Competing interests

   No competing interests declared

3. Aleah M DuBois

   Department of Psychology and Neuroscience, Boston College, Chestnut Hill, United States

   Contribution

   Data curation, Formal analysis

   Competing interests

   No competing interests declared

4. Christa B Michel

   Department of Psychology and Neuroscience, Boston College, Chestnut Hill, United States

   Contribution

   Data curation, Formal analysis

   Competing interests

   No competing interests declared

5. Katherine E Hanrahan

   Department of Psychology and Neuroscience, Boston College, Chestnut Hill, United States

   Contribution

   Data curation, Formal analysis

   Competing interests

   No competing interests declared

6. David C Williams

   Department of Psychology and Neuroscience, Boston College, Chestnut Hill, United States

   Contribution

   Data curation, Formal analysis

   Competing interests

   No competing interests declared

7. Stefano Anzellotti

   Department of Psychology and Neuroscience, Boston College, Chestnut Hill, United States

   Contribution

   Supervision, Investigation, Visualization

   Competing interests

   No competing interests declared

8. Michael A McDannald

   Department of Psychology and Neuroscience, Boston College, Chestnut Hill, United States

   Contribution

   Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing – original draft, Project administration, Writing – review and editing

   For correspondence

   michael.mcdannald@bc.edu

   Competing interests

   No competing interests declared

   Additional information

   Lead contacts

   "This ORCID iD identifies the author of this article:" 0000-0001-8525-1260

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