Experience Modulates Vicarious Freezing in Rats: A Model for Empathy

The study of the neural basis of emotional empathy has received a surge of interest in recent years but mostly employing human neuroimaging. A simpler animal model would pave the way for systematic single cell recordings and invasive manipulations of the brain regions implicated in empathy. Recent evidence has been put forward for the existence of empathy in rodents. In this study, we describe a potential model of empathy in female rats, in which we studied interactions between two rats: a witness observes a demonstrator experiencing a series of footshocks. By comparing the reaction of witnesses with or without previous footshock experience, we examine the role of prior experience as a modulator of empathy. We show that witnesses having previously experienced footshocks, but not naïve ones, display vicarious freezing behavior upon witnessing a cage-mate experiencing footshocks. Strikingly, the demonstrator's behavior was in turn modulated by the behavior of the witness: demonstrators froze more following footshocks if their witness froze more. Previous experiments have shown that rats emit ultrasonic vocalizations (USVs) when receiving footshocks. Thus, the role of USV in triggering vicarious freezing in our paradigm is examined. We found that experienced witness-demonstrator pairs emitted more USVs than naïve witness-demonstrator pairs, but the number of USVs was correlated with freezing in demonstrators, not in witnesses. Furthermore, playing back the USVs, recorded from witness-demonstrator pairs during the empathy test, did not induce vicarious freezing behavior in experienced witnesses. Thus, our findings confirm that vicarious freezing can be triggered in rats, and moreover it can be modulated by prior experience. Additionally, our result suggests that vicarious freezing is not triggered by USVs per se and it influences back onto the behavior of the demonstrator that had elicited the vicarious freezing in witnesses, introducing a paradigm to study empathy as a social loop.

[1]  E. Covey,et al.  Social Transmission of Fear in Rats: The Role of 22-kHz Ultrasonic Distress Vocalization , 2010, PloS one.

[2]  M. Broillet,et al.  Grueneberg Ganglion Cells Mediate Alarm Pheromone Detection in Mice , 2008, Science.

[3]  Stefan M. Brudzynski,et al.  Principles of Rat Communication: Quantitative Parameters of Ultrasonic Calls in Rats , 2005, Behavior genetics.

[4]  B. Galef Direct and Indirect Behavioral Pathways to the Social Transmission of Food Avoidance a , 1985, Annals of the New York Academy of Sciences.

[5]  S. Brudzyński,et al.  Behavioural responses of laboratory rats to playback of 22 kHz ultrasonic calls , 1995, Physiology & Behavior.

[6]  J. Decety,et al.  Gender Differences in the Mu Rhythm of the Human Mirror-Neuron System , 2008, PloS one.

[7]  T. Parrish,et al.  Aversive Learning Enhances Perceptual and Cortical Discrimination of Indiscriminable Odor Cues , 2008, Science.

[8]  G. Rizzolatti,et al.  Action recognition in the premotor cortex. , 1996, Brain : a journal of neurology.

[9]  J. Decety,et al.  A Social-Neuroscience Perspective on Empathy , 2006 .

[10]  Christian Keysers,et al.  Expanding the mirror: vicarious activity for actions, emotions, and sensations , 2009, Current Opinion in Neurobiology.

[11]  G. Ehret Infant Rodent Ultrasounds – A Gate to the Understanding of Sound Communication , 2005, Behavior genetics.

[12]  G. Rizzolatti,et al.  I Know What You Are Doing A Neurophysiological Study , 2001, Neuron.

[13]  Andrew N. Meltzoff,et al.  How do we perceive the pain of others? A window into the neural processes involved in empathy , 2005, NeuroImage.

[14]  Arne D. Ekstrom,et al.  Single-Neuron Responses in Humans during Execution and Observation of Actions , 2010, Current Biology.

[15]  L. Kaczmarek,et al.  Between-subject transfer of emotional information evokes specific pattern of amygdala activation. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[16]  L. Fogassi,et al.  A Touching Sight SII/PV Activation during the Observation and Experience of Touch , 2004, Neuron.

[17]  J. Panksepp,et al.  Breeding for 50-kHz Positive Affective Vocalization in Rats , 2005, Behavior genetics.

[18]  E. Saltzman,et al.  Action Representation of Sound: Audiomotor Recognition Network While Listening to Newly Acquired Actions , 2007, The Journal of Neuroscience.

[19]  F. K. Marcondes,et al.  Estrous cycle influences the response of female rats in the elevated plus-maze test , 2001, Physiology & Behavior.

[20]  C. Frye,et al.  Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progesterone and 3alpha,5alpha-THP. , 2000, Pharmacology, biochemistry, and behavior.

[21]  M Dennis,et al.  Observation and discrimination learning in the rat: specific and nonspecific effects. , 1972, Journal of comparative and physiological psychology.

[22]  T. Kikusui,et al.  Partner's stress status influences social buffering effects in rats. , 2004, Behavioral neuroscience.

[23]  D. Perrett,et al.  Opinion TRENDS in Cognitive Sciences Vol.8 No.11 November 2004 Demystifying social cognition: a Hebbian perspective , 2022 .

[24]  M. Hoffman,et al.  Sex differences in empathy and related behaviors. , 1977, Psychological bulletin.

[25]  S. Baron-Cohen,et al.  Sex differences in human neonatal social perception , 2000 .

[26]  Carolyn E. Jones,et al.  Fear conditioning by-proxy: Social transmission of fear during memory retrieval , 2010, Behavioural Brain Research.

[27]  J. O'Doherty,et al.  Empathic neural responses are modulated by the perceived fairness of others , 2006, Nature.

[28]  L. Fogassi,et al.  Audiovisual mirror neurons and action recognition , 2003, Experimental Brain Research.

[29]  G. Rizzolatti,et al.  Functional Organization of Inferior Parietal Lobule Convexity in the Macaque Monkey: Electrophysiological Characterization of Motor, Sensory and Mirror Responses and Their Correlation with Cytoarchitectonic Areas , 2022 .

[30]  T. H. Brown,et al.  Single-unit responses to 22kHz ultrasonic vocalizations in rat perirhinal cortex , 2007, Behavioural Brain Research.

[31]  J. O'Doherty,et al.  Empathy for Pain Involves the Affective but not Sensory Components of Pain , 2004, Science.

[32]  D. C. Blanchard,et al.  Twenty-two kHz alarm cries to presentation of a predator, by laboratory rats living in visible burrow systems , 1991, Physiology & Behavior.

[33]  Shigeru Watanabe,et al.  An experimental analysis of “empathic” response: Effects of pain reactions of pigeon upon other pigeon's operant behavior. , 1986, Behavioural Processes.

[34]  D. S. Fokkema,et al.  Pair-housing of male and female rats during chronic stress exposure results in gender-specific behavioral responses , 2005, Hormones and Behavior.

[35]  J. Mazziotta,et al.  Neural mechanisms of empathy in humans: A relay from neural systems for imitation to limbic areas , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  J. Decety,et al.  Human Empathy Through the Lens of Social Neuroscience , 2006, TheScientificWorldJournal.

[37]  G. Rizzolatti,et al.  Both of Us Disgusted in My Insula The Common Neural Basis of Seeing and Feeling Disgust , 2003, Neuron.

[38]  R. Church Emotional reactions of rats to the pain of others. , 1959, Journal of comparative and physiological psychology.

[39]  Salvatore Maria Aglioti,et al.  Stimulus-driven modulation of motor-evoked potentials during observation of others' pain , 2006, NeuroImage.

[40]  D. Dietz,et al.  Sex Differences in Social Interaction in Rats: Role of the Immediate-Early Gene zif268 , 2010, Neuropsychopharmacology.

[41]  C. Keysers,et al.  Empathy and the Somatotopic Auditory Mirror System in Humans , 2006, Current Biology.

[42]  G. Pellegrino,et al.  Vicarious responses to pain in anterior cingulate cortex: Is empathy a multisensory issue? , 2004, Cognitive, affective & behavioral neuroscience.

[43]  B. Prendergast,et al.  Sex-specific social regulation of inflammatory responses and sickness behaviors , 2010, Brain, Behavior, and Immunity.

[44]  Christian Keysers,et al.  Somatosensation in social perception , 2010, Nature Reviews Neuroscience.

[45]  F. D. de Waal Putting the altruism back into altruism: the evolution of empathy. , 2008, Annual review of psychology.

[46]  Christian Keysers,et al.  Inferior frontal gyrus activity triggers anterior insula response to emotional facial expressions. , 2008, Emotion.

[47]  C. Frye,et al.  Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progesterone and 3α,5α-THP , 2000, Pharmacology Biochemistry and Behavior.

[48]  Daniel J. Levitin,et al.  Social Modulation of Pain as Evidence for Empathy in Mice , 2006, Science.

[49]  S. Baron-Cohen,et al.  The Empathy Quotient: An Investigation of Adults with Asperger Syndrome or High Functioning Autism, and Normal Sex Differences , 2004, Journal of autism and developmental disorders.

[50]  T. Bredy,et al.  Social modulation of associative fear learning by pheromone communication. , 2008, Learning & memory.

[51]  Garet P Lahvis,et al.  Empathy Is Moderated by Genetic Background in Mice , 2009, PloS one.

[52]  Rebecca C. Knickmeyer,et al.  Sex Differences in the Brain: Implications for Explaining Autism , 2005, Science.

[53]  C. Keysers,et al.  Evidence for mirror systems in emotions , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[54]  R. Schwarting,et al.  Overt behavior and ultrasonic vocalization in a fear conditioning paradigm: A dose–response study in the rat , 2005, Neurobiology of Learning and Memory.

[55]  H. Ruley,et al.  Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC , 2010, Nature Neuroscience.

[56]  S. Preston,et al.  Empathy: Its ultimate and proximate bases. , 2001, The Behavioral and brain sciences.

[57]  J. King,et al.  Female fear: Influence of estrus cycle on behavioral response and neuronal activation , 2009, Behavioural Brain Research.

[58]  G. Rizzolatti,et al.  Parietal Lobe: From Action Organization to Intention Understanding , 2005, Science.

[59]  Atsushi Iriki,et al.  Social cognition in premotor and parietal cortex , 2008, Social neuroscience.

[60]  B G Galef,et al.  Aversive and attractive marking of toxic and safe foods by Norway rats. , 1985, Behavioral and neural biology.

[61]  David J. Anderson,et al.  Neural Correlates of Competing Fear Behaviors Evoked by an Innately Aversive Stimulus , 2003, The Journal of Neuroscience.

[62]  G. Rizzolatti,et al.  Mirror Neurons Differentially Encode the Peripersonal and Extrapersonal Space of Monkeys , 2009, Science.

[63]  J. Panksepp,et al.  50-kHz chirping (laughter?) in response to conditioned and unconditioned tickle-induced reward in rats: effects of social housing and genetic variables , 2000, Behavioural Brain Research.

[64]  Lauren K. Jones,et al.  Asymmetrical stimulus generalization following differential fear conditioning , 2008, Neurobiology of Learning and Memory.

[65]  S. Brudzyński Ultrasonic calls of rats as indicator variables of negative or positive states: Acetylcholine–dopamine interaction and acoustic coding , 2007, Behavioural Brain Research.

[66]  C. Keysers,et al.  A Common Anterior Insula Representation of Disgust Observation, Experience and Imagination Shows Divergent Functional Connectivity Pathways , 2008, PloS one.

[67]  O. Tzeng,et al.  Sex differences in the neuroanatomy of human mirror-neuron system: A voxel-based morphometric investigation , 2009, Neuroscience.

[68]  T R Zentall,et al.  Observational Learning and Social Facilitation in the Rat , 1972, Science.

[69]  G. J. Horst,et al.  Gender-specific effects of social housing in rats after chronic mild stress exposure , 2003, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[70]  Nancy Eisenberg,et al.  Sex Differences in Empathy and Related Capacities , 1983 .

[71]  G. Alexander,et al.  Sex differences in response to children's toys in nonhuman primates (Cercopithecus aethiops sabaeus) , 2002 .

[72]  Christian Keysers,et al.  Testing Simulation Theory with Cross-Modal Multivariate Classification of fMRI Data , 2008, PloS one.

[73]  Akira Masuda,et al.  Social Transmission of Avoidance Behavior under Situational Change in Learned and Unlearned Rats , 2009, PloS one.

[74]  T. Singer,et al.  The Social Neuroscience of Empathy , 2009, Annals of the New York Academy of Sciences.

[75]  J. Dostrovsky,et al.  Pain-related neurons in the human cingulate cortex , 1999, Nature Neuroscience.

[76]  T. Singer,et al.  The empathic brain: how, when and why? , 2006, Trends in Cognitive Sciences.

[77]  J. Neumaier,et al.  Differential effects of ovarian steroids on anxiety versus fear as measured by open field test and fear-potentiated startle , 2006, Behavioural Brain Research.

[78]  G. Rizzolatti,et al.  Hearing Sounds, Understanding Actions: Action Representation in Mirror Neurons , 2002, Science.

[79]  Christian Keysers,et al.  Empathy for positive and negative emotions in the gustatory cortex , 2007, NeuroImage.

[80]  Stephen Maren,et al.  Social modulation of learning in rats. , 2010, Learning & memory.

[81]  C. Keysers,et al.  Towards a unifying neural theory of social cognition. , 2006, Progress in brain research.