Audible pain squeaks can mediate emotional contagion across pre-exposed rats with a potential effect of auto-conditioning.

Footshock self-experience enhances rodents' reactions to the distress of others. Here, we tested one potential mechanism supporting this phenomenon, namely that animals auto-condition to their own pain squeaks during shock pre-exposure. In Experiment 1, shock pre-exposure increased freezing and 22 kHz distress vocalizations while animals listened to the audible pain-squeaks of others. In Experiment 2 and 3, to test the auto-conditioning theory, we weakened the noxious pre-exposure stimulus not to trigger pain squeaks, and compared pre-exposure protocols in which we paired it with squeak playback against unpaired control conditions. Although all animals later showed fear responses to squeak playbacks, these were weaker than following typical pre-exposure (Experiment 1) and not stronger following paired than unpaired pre-exposure. Experiment 1 thus demonstrates the relevance of audible pain squeaks in the transmission of distress but Experiment 2 and 3 highlight the difficulty to test auto-conditioning: stimuli weak enough to decouple pain experience from hearing self-emitted squeaks are too weak to trigger the experience-dependent increase in fear transmission that we aimed to study. Although our results do not contradict the auto-conditioning hypothesis, they fail to disentangle it from sensitization effects. Future studies could temporarily deafen animals during pre-exposure to further test this hypothesis.

Intracranial human recordings reveal association between neural activity and perceived intensity for the pain of others in the insula.

Based on neuroimaging data, the insula is considered important for people to empathize with the pain of others. Here, we present intracranial electroencephalographic (iEEG) recordings and single-cell recordings from the human insula while seven epilepsy patients rated the intensity of a woman's painful experiences seen in short movie clips. Pain had to be deduced from seeing facial expressions or a hand being slapped by a belt. We found activity in the broadband 20-190 Hz range correlated with the trial-by-trial perceived intensity in the insula for both types of stimuli. Within the insula, some locations had activity correlating with perceived intensity for our facial expressions but not for our hand stimuli, others only for our hand but not our face stimuli, and others for both. The timing of responses to the sight of the hand being hit is best explained by kinematic information; that for our facial expressions, by shape information. Comparing the broadband activity in the iEEG signal with spiking activity from a small number of neurons and an fMRI experiment with similar stimuli revealed a consistent spatial organization, with stronger associations with intensity more anteriorly, while viewing the hand being slapped.

Paw preference is associated with behavioural despair and spatial reference memory in male rats.

Paw preference, one of the well-studied behavioural markers of asymmetry, has been associated with affective states and pathologies such as behavioural despair, a rodent model of clinical depression. However, a consistent differential effect of paw preference has not been observed for cognitive functions. In order to investigate the affective properties of paw preference together with its potential cognitive effects, we grouped male Wistar rats as left- or right-pawed, and tested them in the forced swim test and Morris water maze for behavioural despair and spatial memory performance, respectively. We found that left-pawed rats were significantly more susceptible to behavioural despair, while spatial learning performance of the two groups were not different over a five-day Morris water maze task. Left-pawed rats, however, displayed a better reference memory than the right-pawed ones on the subsequent probe trial when the hidden platform of the maze was removed. These findings indicate paw preference as a vulnerability factor for behavioural despair and reveal a previously unknown association between left-paw preference and reference memory performance as assessed in the probe trial of the Morris water maze.

Harm to Others Acts as a Negative Reinforcer in Rats.

Empathy, the ability to share another individual's emotional state and/or experience, has been suggested to be a source of prosocial motivation by attributing negative value to actions that harm others. The neural underpinnings and evolution of such harm aversion remain poorly understood. Here, we characterize an animal model of harm aversion in which a rat can choose between two levers providing equal amounts of food but one additionally delivering a footshock to a neighboring rat. We find that independently of sex and familiarity, rats reduce their usage of the preferred lever when it causes harm to a conspecific, displaying an individually varying degree of harm aversion. Prior experience with pain increases this effect. In additional experiments, we show that rats reduce the usage of the harm-inducing lever when it delivers twice, but not thrice, the number of pellets than the no-harm lever, setting boundaries on the magnitude of harm aversion. Finally, we show that pharmacological deactivation of the anterior cingulate cortex, a region we have shown to be essential for emotional contagion, reduces harm aversion while leaving behavioral flexibility unaffected. This model of harm aversion might help shed light onto the neural basis of psychiatric disorders characterized by reduced harm aversion, including psychopathy and conduct disorders with reduced empathy, and provides an assay for the development of pharmacological treatments of such disorders. VIDEO ABSTRACT.

Bidirectional cingulate-dependent danger information transfer across rats.

Social transmission of freezing behavior has been conceived of as a one-way phenomenon in which an observer "catches" the fear of another. Here, we use a paradigm in which an observer rat witnesses another rat receiving electroshocks. Bayesian model comparison and Granger causality show that rats exchange information about danger in both directions: how the observer reacts to the demonstrator's distress also influences how the demonstrator responds to the danger. This was true to a similar extent across highly familiar and entirely unfamiliar rats but is stronger in animals preexposed to shocks. Injecting muscimol in the anterior cingulate of observers reduced freezing in the observers and in the demonstrators receiving the shocks. Using simulations, we support the notion that the coupling of freezing across rats could be selected for to more efficiently detect dangers in a group, in a way similar to cross-species eavesdropping.

Rapid and long-lasting improvements in neural discrimination of acoustic signals with passive familiarization.

Sensory representations in the adult brain must undergo dynamic changes to adapt to the complexity of the external world. This study investigated how passive exposure to novel sounds modifies neural representations to facilitate recognition and discrimination, using the zebra finch model organism. The neural responses in an auditory structure in the zebra finch brain, Caudal Medial Nidopallium (NCM), undergo a long-term form of adaptation with repeated stimulus presentation, providing an excellent substrate to probe the neural underpinnings of adaptive sensory representations. In Experiment 1, electrophysiological activity in NCM was recorded under passive listening conditions as novel natural vocalizations were familiarized through playback. Neural decoding of stimuli using the temporal profiles of both single-unit and multi-unit responses improved dramatically during the first few stimulus presentations. During subsequent encounters, these signals were recognized after hearing fewer initial acoustic features. Remarkably, the accuracy of neural decoding was higher when different stimuli were heard in separate blocks compared to when they were presented randomly in a shuffled sequence. NCM neurons with narrow spike waveforms generally yielded higher neural decoding accuracy than wide spike neurons, but the rate at which these accuracies improved with passive exposure was comparable between the two neuron types. Experiment 2 supported and extended these findings by showing that the rapid gains in neural decoding of novel vocalizations with passive familiarization were long-lasting, maintained for 20 hours after the initial encounter, in multi-unit responses. Taken together, these findings provide valuable insights into the mechanisms by which the nervous system dynamically modulates sensory representations to improve discrimination of novel complex signals over short and long timescales. Similar mechanisms may also be engaged during processing of human speech signals, and thus may have potential translational relevance for elucidating the neural basis of speech comprehension difficulties.

Head-turning asymmetry: A novel lateralization in rats predicts susceptibility to behavioral despair.

Behavioral markers of laterality reflecting underlying neurobiological asymmetries between the cerebral hemispheres are related to differential susceptibility to mood disorders. In the present study, we investigated the strength and consistency of a novel behavioral lateralization, head-turning asymmetry, and its relation to behavioral despair in adult female Wistar rats. Head-turning biases were determined in a test where water-deprived rats had to turn their head to right or left to gain access to a water dispenser. This procedure was administered 4 times over 8days. Four days after the head-turning test, rats were subjected to two forced swim tests separated by 24h to examine the relationship between head-turning asymmetry and behavioral despair. Rats were administered one more head-turning test session after the second swim test to determine whether behavioral despair induction altered head-turning direction preferences. Results revealed significant correlations among head-turning test sessions indicating head-turning direction preference as measured with our method is a consistent behavioral lateralization. Although most rats were strongly lateralized, there was no bias in either direction at the population level. Importantly, we found that while rats with a left head-turning bias showed a significant increase in the duration of immobility from the first to the second swim test, right-biased rats performed similarly in the two swim tests. Behavioral despair induction did not change head-turning direction preferences. The present findings show that head-turning asymmetries are predictive of mood disorders in rats and may serve as the basis to elucidate the mechanisms relating hemispheric asymmetries to depression in humans.

Principles of auditory processing differ between sensory and premotor structures of the songbird forebrain.

Sensory and motor brain structures work in collaboration during perception. To evaluate their respective contributions, the present study recorded neural responses to auditory stimulation at multiple sites simultaneously in both the higher-order auditory area NCM and the premotor area HVC of the songbird brain in awake zebra finches (Taeniopygia guttata). Bird's own song (BOS) and various conspecific songs (CON) were presented in both blocked and shuffled sequences. Neural responses showed plasticity in the form of stimulus-specific adaptation, with markedly different dynamics between the two structures. In NCM, the response decrease with repetition of each stimulus was gradual and long-lasting and did not differ between the stimuli or the stimulus presentation sequences. In contrast, HVC responses to CON stimuli decreased much more rapidly in the blocked than in the shuffled sequence. Furthermore, this decrease was more transient in HVC than in NCM, as shown by differential dynamics in the shuffled sequence. Responses to BOS in HVC decreased more gradually than to CON stimuli. The quality of neural representations, computed as the mutual information between stimuli and neural activity, was higher in NCM than in HVC. Conversely, internal functional correlations, estimated as the coherence between recording sites, were greater in HVC than in NCM. The cross-coherence between the two structures was weak and limited to low frequencies. These findings suggest that auditory communication signals are processed according to very different but complementary principles in NCM and HVC, a contrast that may inform study of the auditory and motor pathways for human speech processing.NEW & NOTEWORTHY Neural responses to auditory stimulation in sensory area NCM and premotor area HVC of the songbird forebrain show plasticity in the form of stimulus-specific adaptation with markedly different dynamics. These two structures also differ in stimulus representations and internal functional correlations. Accordingly, NCM seems to process the individually specific complex vocalizations of others based on prior familiarity, while HVC responses appear to be modulated by transitions and/or timing in the ongoing sequence of sounds.

Right-but not left-paw use in female rats provides advantage in forced swim tests.

Left- and right-pawed adult female Wistar rats were subjected to forced swimming on two consecutive days. Compared to the right-pawed group, left- pawed rats displayed significantly increased immobility from the first to the second swim test and remained significantly more immobile in the second swim test. Both groups performed similarly in spatial learning in the Morris water maze suggesting that left- pawed rats are differentially and specifically susceptible to depressogenic treatment.