Rats respond to aversive emotional arousal of human handlers with the activation of the basolateral and central amygdala

Abstract

Reading danger signals may save an animal's life, and learning about threats from others allows avoiding first-hand aversive and often fatal experiences. Fear expressed by other individuals, including those belonging to other species, may indicate the presence of a threat in the environment and is an important social cue. Humans and other animals respond to conspecifics' fear with increased activity of the amygdala, the brain structure crucial for detecting threats and mounting an appropriate response to them. It is unclear, however, whether the cross-species transmission of threat information involves similar mechanisms, e.g., whether animals respond to the aversively induced emotional arousal of humans with activation of fear-processing circuits in the brain. Here, we report that when rats interact with a human caregiver who had recently undergone fear conditioning, they show risk assessment behavior and enhanced amygdala activation. The amygdala response involves its two major parts, the basolateral and central, which detect a threat and orchestrate defensive responses. Further, we show that humans who learn about a threat by observing another aversively aroused human, similar to rats, activate the basolateral and centromedial parts of the amygdala. Our results demonstrate that rats detect the emotional arousal of recently aversively stimulated caregivers and suggest that cross-species social transmission of threat information may involve similar neural circuits in the amygdala as the within-species transmission.

Keywords: basolateral amygdala; centromedial amygdala; cross-species; interspecies; social transmission of threat information.

Fig. 1.

Experimental design and rat behavioral results. (A) During the first 5 d, every human caregiver handled four rats (2 sessions involving 2 rats): First, they kept their hands on the edge of the cage for 40 s and then took the rats into the arms and handled them for 2 min, both at the same time. (B) On day 6, mild vibrations were applied to the caregiver during the computer task, and only rats from the control (marked in green) cage were handled. (C) On day 7, uncomfortable electric shocks were applied to the caregiver during the computer task, and only rats from the experimental (marked in pink) cage were handled. (D) Rats’ behavior during 40 s in the cage with the caregivers holding their hands on the edge of the cage (phase 1) followed by the period during which the humans handled the two rats (phase 2, divided into two 60-s blocks). Colors mark the rats interacting with the caregivers on day 6 (green) and 7 (pink). Rats exposed to aversively aroused caregivers interacted less with human hands and spent more time exploring the cage. The dashed line divides the arms phase into two 60-s periods. Error bars indicate SEM; n_exp = 18; n_ctrl = 18. (E) Mean durations of a single USV episode (n_exp = 15, n_ctrl = 15; USV from five cages measured in three time points; one extreme outlier excluded from the graph for visualization purposes) and the USV frequency indicative of appetitive signaling (n_exp = 3, n_ctrl = 9). USV data were recorded in pairs of rats at three time points. Error bars indicate SEM.

Fig. 2.

(A) Rat amygdala activations following interaction with human caregivers. Error bars indicate SEM; n_La-ctrl = 49, n_La-exp = 41, n_BA-ctrl = 61, n_BA-exp = 55, n_CeAl-ctrl = 60, n_CeAl-exp = 52, n_CeAm-ctrl = 61, n_CeAm-exp = 52, n_MeA-ctrl = 59, n_MeA-exp = 50; n indicates the number of brain sections analyzed in 18 rats in each group. (B) The sample brain sections showing c-Fos expression in the rats interacting with caregivers subjected to the sham procedure (Left) and with aversively aroused caregivers (Right). The upper part shows five main amygdalar nuclei: La: lateral, BA: basal, CeAl: central, lateral division, CeAm: central, medial division, MeA: medial. In the lower part, the central (central lateral + central medial, CeA) and basal (BA) parts are zoomed in.

Fig. 3.

Fear transfer between humans. (A) In the neuroimaging experiment, pairs of friends were invited to the lab. (B) The observer was lying in the functional MRI (fMRI) scanner and watching his friend (the demonstrator) performing the fear conditioning task. (C) The task consisted of two squares presented one by one, one of which was repeatedly paired with an uncomfortable electric shock applied to the forearm. (D) Centromedial (CM, green) and basolateral (BL, orange) amygdala were activated in the observers; US > no US contrast, small volume corrected within the CM and BL masks, N = 48.

Fig. 4.

Aversively aroused partner activated the centromedial and basolateral amygdala in rats (human–rat interaction) and humans (human–human interaction). (A) The mean c-Fos expression was higher in the rats interacting with caregivers who had undergone fear conditioning (EXP) compared to the rats interacting with caregivers subjected to the sham procedure (CTRL), n_CM-ctrl = 61, n_CM-exp = 52, n_BL-ctrl = 61, n_BL-exp = 55, n indicates the number of brain sections analyzed in 18 rats in each group. (B) In humans, the BOLD signal was increased in response to the US applied to the interaction partner compared to the no US condition. Error bars extend to data points placed no further than 1.5*IQR (interquartile range) beyond the 1st quartile and above the 3rd quartile, N = 48.