Similarities and differences in the functional architecture of mother- infant communication in rhesus macaque and British mother-infant dyads.

Similarly to humans, rhesus macaques engage in mother-infant face-to-face interactions. However, no previous studies have described the naturally occurring structure and development of mother-infant interactions in this population and used a comparative-developmental perspective to directly compare them to the ones reported in humans. Here, we investigate the development of infant communication, and maternal responsiveness in the two groups. We video-recorded mother-infant interactions in both groups in naturalistic settings and analysed them with the same micro-analytic coding scheme. Results show that infant social expressiveness and maternal responsiveness are similarly structured in humans and macaques. Both human and macaque mothers use specific mirroring responses to specific infant social behaviours (modified mirroring to communicative signals, enriched mirroring to affiliative gestures). However, important differences were identified in the development of infant social expressiveness, and in forms of maternal responsiveness, with vocal responses and marking behaviours being predominantly human. Results indicate a common functional architecture of mother-infant communication in humans and monkeys, and contribute to theories concerning the evolution of specific traits of human behaviour.

Two different mirror neuron networks: The sensorimotor (hand) and limbic (face) pathways.

The vast majority of functional studies investigating mirror neurons (MNs) explored their properties in relation to hand actions, and very few investigated how MNs respond to mouth actions or communicative gestures. Since hand and mouth MNs were recorded in two partially overlapping sectors of the ventral precentral cortex of the macaque monkey, there is a general assumption that they share a same neuroanatomical network, with the parietal cortex as a main source of visual information. In the current review, we challenge this perspective and describe the connectivity pattern of mouth MN sector. The mouth MNs F5/opercular region is connected with premotor, parietal areas mostly related to the somatosensory and motor representation of the face/mouth, and with area PrCO, involved in processing gustatory and somatosensory intraoral input. Unlike hand MNs, mouth MNs do not receive their visual input from parietal regions. Such information related to face/communicative behaviors could come from the ventrolateral prefrontal cortex. Further strong connections derive from limbic structures involved in encoding emotional facial expressions and motivational/reward processing. These brain structures include the anterior cingulate cortex, the anterior and mid-dorsal insula, orbitofrontal cortex and the basolateral amygdala. The mirror mechanism is therefore composed and supported by at least two different anatomical pathways: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and is connected with limbic structures, involved in communication/emotions and reward processing.

Frequency and topography in monkey electroencephalogram during action observation: possible neural correlates of the mirror neuron system.

The observation of actions executed by others results in desynchronization of electroencephalogram (EEG) in the alpha and beta frequency bands recorded from the central regions in humans. On the other hand, mirror neurons, which are thought to be responsible for this effect, have been studied only in macaque monkeys, using single-cell recordings. Here, as a first step in a research programme aimed at understanding the parallels between human and monkey mirror neuron systems (MNS), we recorded EEG from the scalp of two monkeys during action observation. The monkeys were trained to fixate on the face of a human agent and subsequently to fixate on a target upon which the agent performed a grasping action. We found that action observation produced desynchronization in the 19-25 Hz band that was strongest over anterior and central electrodes. These results are in line with human data showing that specific frequency bands within the power spectrum of the ongoing EEG may be modulated by observation of actions and therefore might be a specific marker of MNS activity.

Individual and social learning processes involved in the acquisition and generalization of tool use in macaques.

Macaques can efficiently use several tools, but their capacity to discriminate the relevant physical features of a tool and the social factors contributing to their acquisition are still poorly explored. In a series of studies, we investigated macaques' ability to generalize the use of a stick as a tool to new objects having different physical features (study 1), or to new contexts, requiring them to adapt the previously learned motor strategy (study 2). We then assessed whether the observation of a skilled model might facilitate tool-use learning by naive observer monkeys (study 3). Results of study 1 and study 2 showed that monkeys trained to use a tool generalize this ability to tools of different shape and length, and learn to adapt their motor strategy to a new task. Study 3 demonstrated that observing a skilled model increases the observers' manipulations of a stick, thus facilitating the individual discovery of the relevant properties of this object as a tool. These findings support the view that in macaques, the motor system can be modified through tool use and that it has a limited capacity to adjust the learnt motor skills to a new context. Social factors, although important to facilitate the interaction with tools, are not crucial for tool-use learning.

Contagious yawning in gelada baboons as a possible expression of empathy.

Yawn contagion in humans has been proposed to be related to our capacity for empathy. It is presently unclear whether this capacity is uniquely human or shared with other primates, especially monkeys. Here, we show that in gelada baboons (Theropithecus gelada) yawning is contagious between individuals, especially those that are socially close, i.e., the contagiousness of yawning correlated with the level of grooming contact between individuals. This correlation persisted after controlling for the effect of spatial association. Thus, emotional proximity rather than spatial proximity best predicts yawn contagion. Adult females showed precise matching of different yawning types, which suggests a mirroring mechanism that activates shared representations. The present study also suggests that females have an enhanced sensitivity and emotional tuning toward companions. These findings are consistent with the view that contagious yawning reveals an emotional connection between individuals. This phenomenon, here demonstrated in monkeys, could be a building block for full-blown empathy.

From monkey mirror neurons to primate behaviours: possible 'direct' and 'indirect' pathways.

The discovery of mirror neurons (MNs), deemed to be at the basis of action understanding, could constitute the potential solution to the 'correspondence problem' between one's own and others' action that is crucial for of imitative behaviours. However, it is still to be clarified whether, and how, several imitative phenomena, differing in terms of complexity and cognitive effort, could be explained within a unified framework based on MNs. Here we propose that MNs could differently contribute to distinct imitative behaviours by means of two anatomo-functional pathways, subjected to changes during development. A 'direct mirror pathway', directly influencing the descending motor output, would be responsible for neonatal and automatic imitation. This proposal is corroborated by some new behavioural evidences provided here. During development, the increased control of voluntary movements and the capacity to efficiently suppress automatic motor activation during action observation assign to the core MNs regions essentially perceptuo-cognitive functions. These functions would be exploited by an 'indirect mirror pathway' from the core regions of the MN system to prefrontal cortex. This latter would play a key role in parsing, storing and organizing motor representations, allowing the emergence of more efficient and complex imitative behaviours such as response facilitation and true imitation.

The observation and hearing of eating actions activates motor programs related to eating in macaque monkeys.

The observation of actions can lead, in some cases, to the repetition of those same actions. In other words, motor programs similar to those observed can be recruited. Since this phenomenon is expressed when in the presence of another individual, it has been named social facilitation. In the present study we investigated whether the observation and/or hearing of eating actions facilitate eating behaviors in observing/listening pig-tailed macaques. In experiment 1, the observation of an eating room mate significantly enhanced eating behavior in the observer. Similar results were obtained (experiment 2) in response to the sound of eating actions but not to control sounds (experiment 3). We propose that eating facilitation triggered by observation or listening of eating actions can rely on the mirror neuron system of ventral premotor cortex that provides a matching between the observed/listened action and the executed action. This matching system can subsequently trigger the motor programs necessary for repeating the observed/heard actions.

Accumbal dopamine and serotonin in anticipation of the next aggressive episode in rats.

Autonomic and limbic neural activities are linked to aggressive behavior, and it is hypothesized that activities in the cardiovascular and monoaminergic systems play a role in preparing for an aggressive challenge. The objective was to learn about the emergence of monoamine activity in nucleus accumbens before an aggressive confrontation that was omitted at the regular time of occurrence, dissociating the motoric from the aminergic activity. Dopamine, serotonin, heart rate and behavioral activity were monitored before, during and after a single 10-min confrontation in resident male Long-Evans rats fitted with a microdialysis probe in the n. accumbens and with a telemetry sender (experiment 1). DA, but not 5-HT efflux, was confirmed to increase in n. accumbens during and after a single aggressive episode. In aggressive males that confronted an opponent daily for 10 days (experiment 2) heart rate rose 1 h before the regularly scheduled encounter relative to control rats, as measured on day 11 in the absence of any aggression. Concurrently, DA levels increased by 60-70% over baseline levels and 5-HT levels decreased by 30-35% compared to baseline levels. These changes were sustained over 1 h, and contrasted with no significant changes in DA, 5-HT, heart rate or behavioral activity in control rats. The rise in mesolimbic DA appears to be significant in anticipating the physiological and behavioral demands of an aggressive episode, and the fall in 5-HT in its termination, dissociated from the actual execution of the behavior.

Cardiac autonomic responses to intermittent social conflict in rats.

Intermittent exposure to the same stressor can lead to a gradual decline in physiological, neuroendocrine and behavioral stress responses (habituation). We investigated possible habituation of cardiac autonomic responsiveness and susceptibility to cardiac arrhythmias in male rats exposed to either intermittent social victory (VIC) or defeat (DEF) stress (10 exposures in each case). Electrocardiograms were recorded via radiotelemetry and the sympathovagal balance at the level of the heart was evaluated via time-domain measurements of heart rate variability, namely average R--R interval (average time interval between two consecutive heart beats, RR), the standard deviation of RR (SD(RR)) and the root-mean-square of successive R--R interval differences (r-MSSD). Values of these parameters were significantly lower in DEF as compared to VIC rats in the second part of the test period (from Minute 6 to Minute 15), suggesting a more pronounced sympathetic dominance in the former group of animals. Accordingly, the occurrence of the most frequent cardiac arrhythmias (ventricular and supraventricular premature beats) was higher in DEF rats. Habituation of cardiac autonomic responsivity was observed across repeated exposure to victory, both in terms of sympathovagal balance and susceptibility to cardiac tachyarrhythmias, whereas no habituation was found in repeatedly defeated animals. A possible explanation to this discrepancy could be the different degree of controllability characterizing the two social challenging situations.

The ability to follow eye gaze and its emergence during development in macaque monkeys.

The ability of monkeys to follow the gaze of other individuals is a matter of debate in many behavioral studies. Physiological studies have shown that in monkeys, as in humans, there are neural correlates of eye direction detection. There is little evidence at the behavioral level, however, of the presence and development of such abilities in monkeys. The aim of the present study was to assess in juveniles and adult pig-tailed macaques (Macaca nemestrina) the capacity to use eye cues only to follow the gaze of an experimenter. Biological stimuli (head, eye, and trunk movements) were presented by an experimenter to 2 adult monkeys with their heads restrained (Experiment 1) and to 11 monkeys of different ages, free to move in their home cages (Experiment 2). A nonbiological stimulus served as a control. Results showed that macaques can follow the gaze of the experimenter by using head/eye and eye cues alone. Trunk movements and nonbiological stimuli did not significantly elicit similar reactions. Juvenile monkeys were not able to orient their attention on the basis of eye cues alone. In general, gaze following was more frequent in adults than in juveniles. Like in humans, however, such abilities in macaques dramatically improve with age suggesting that the transition to adulthood is a crucial period in the development of gaze-following behavior.

Distress vocalizations in maternally separated mouse pups: modulation via 5-HT(1A), 5-HT(1B) and GABA(A) receptors.

RATIONALE: Young rodents emit ultrasonic vocalizations (USVs) when separated from their dams and littermates. Pharmacological agents that act on GABA(A) and/or 5-HT receptors and that alleviate anxiety in humans reduce the emission of these calls. OBJECTIVES: 1) to investigate specific 5-HT1 receptor subtypes that modulate maternal separation-induced USVs in mice; 2) to assess the behavioral specificity of these effects; and 3) to compare 5-HT1 agonists with a positive neurosteroid modulator of the GABA(A) receptor complex. METHODS: Seven-day old CFW mouse pups were isolated from their littermates and placed onto a 20 degrees C surface for 4 min. USVs between 30 and 80 kHz, grid crossing, and rectal temperature were measured in separate groups of mouse pups following subcutaneous administration of 5-HT1A and 5-HT1B receptor agonists and antagonists, the neurosteroid allopregnanolone, or the benzodiazepine midazolam. RESULTS: The 5-HT1A agonists (+)8-OH-DPAT (0.01-0.1 mg/kg) and flesinoxan (0.3-1.0 mg/kg), the selective 5-HT1B agonist CP-94,253 (0.03-30.0 mg/kg), and the mixed 5-HT1B/2C receptor agonist TFMPP (0.1-10.0 mg/kg) dose-dependently reduced USVs. These effects were reversed by the 5-HT1A receptor antagonist WAY 100,635 (0.1 mg/kg) or the 5-HT1B/D receptor antagonist GR 127935 (0.1 mg/kg). The effects of TFMPP were biphasic; low doses (i.e. 0.01 and 0.03 mg/kg) increased the rate of vocalization. Midazolam and allopregnanolone also reduced USVs. The highest doses of flesinoxan, (+)8-OH-DPAT, and allopregnanolone suppressed locomotion, whereas CP-94,253, TFMPP, and midazolam stimulated motor activity. CONCLUSIONS: These experiments confirm that agonists at the 5-HT1 receptors and a positive allosteric modulator of the GABA(A) receptor complex decrease maternal separation-induced USVs in mice, with 5-HT1B manipulations dissociating the effects on vocalizations from sedative effects.

Behavioral profile of wild mice in the elevated plus-maze test for anxiety.

Systematic observations of the defensive behavior of wild rodents have greatly informed the experimental study of anxiety and its neural substrates in laboratory animals. However, as the former work has been almost exclusively carried out in rats, few data are available concerning the reactivity of wild mice to standardized tests of anxiety-related behavior. In the present experiments, we employed ethological measures to examine the behavioral responses of a wild-derived population of house mice (Mus musculus) in the elevated plus-maze. In direct comparisons with laboratory Swiss mice, male wild mice exhibited substantially elevated levels of exploratory activities and an overall "preference" for the open arms of the plus-maze. On re-exposure to the plus-maze, male wild mice showed further increases in open arm exploration, while Swiss mice showed a marked shift to the enclosed parts of the plus-maze. Tested over a single session, female wild mice also exhibited a profile of high open arm exploration, but showed levels of exploratory behaviors and locomotor activity similar to female Swiss counterparts. While exploratory patterns in wild mice show similarities to profiles seen in certain laboratory strains (e.g., BALB/c), wild mice displayed a number of additional behaviors that are unprecedented in plus-maze studies with laboratory mice. These included actual and attempted jumps from the maze, spontaneous freezing, and exploration of the upper ledges of the closed arms. Thus, while in conventional terms the behavior of wild mice was consistent with one of low anxiety-like behavior, the presence of these unique elements instead indicates a profile more accurately characterized by high reactivity and escape motivation. We discuss how the use of an ethological approach to measuring plus-maze behavior can support accurate interpretation of other exceptional profiles in this test, such as those possibly arising from phenotyping of transgenic and gene knockout mice.

Selection, evolution of behavior and animal models in behavioral neuroscience.

We investigated whether genetic differences in various forms of intraspecific aggression and anxiety in four different genetic lines of mice (i.e. wild, outbred Swiss-CD1, inbred DBA/2 and inbred C57/BL6N) may reflect modifications in behavioral strategy. Experiments 1 and 2 used ethologically based paradigms to analyze aggressive and anxiety responses both in social (i.e. aggression) and non-social (i.e. novel environment exploration) contexts. In Experiment 3, an anxiolytic drug (chlordiazepoxide (CDP)) was used to examine possible differences in proximal mechanisms underlying anxiety-related behaviors. The data show that intrasexual aggression, infanticide and maternal aggressions are related and covarying. Genetic lines with the highest levels of intermale attack (i.e. Wild and Swiss-CD1) also have highest levels of infanticide, interfemale attack and maternal aggression but, interestingly, the lowest levels of anxiety. In fact, exploratory behavior is lower and risk assessment behavior markedly higher in DBA/2 and C57/BL6N mice (i.e. the less aggressive strains) compared to Swiss and Wild genetic lines. Although reproductive status influences anxiety levels in female mice, our findings show that (contrary to previous studies) lactating mice are more anxious than virgin females in terms of risk assessment activities. These data demonstrate the importance of studying behavior in a more ecologically-relevant context which emphasizes the function of behavior in a specific situation. Moreover, differential strain sensitivity to the behavioral effects of CDP suggests that genetic lines of mice may differ in the underlying mechanisms mediating behavior. It is therefore possible that artificial selection of different genotypes has resulted in differences in proximate mechanisms modulating the levels of aggression and anxiety, thereby leading to modification of social behavior. Overall, the results presented here suggest that subtle genetic alterations in specific underlying neural mechanisms are likely to cause profound effects on behavioral responses and their adaptive significance. Implications for behavioral neuroscience research that seeks to understand both the proximal and ultimate mechanisms of behavior are discussed.

The influence of gender and age on neonatal rat hypothalamic 5-HT1A and 5-HT2A receptors.

1. Rat hypothalamic 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) concentrations are transiently sexually differentiated in the second week postpartum (pp), with higher levels in the female. In this report we investigate the possibility that 5-HT receptors may also exhibit sexual dimorphism in the neonatal period. 2. 5-HT1A and 5-HT2A receptors were quantitated by radioligand binding of [3H]ketanserin and [3H]8-OH DPAT, respectively, in hypothalamus and amygdala from male and female rats at days 8-16 pp. 3. There was no sexual dimorphism or change in the density of 5-HT2A binding in hypothalamus or amygdala over days 8-16 pp. There was also no sexual dimorphism of 5-HT1A receptors. 4. There was an increase in 5-HT1A receptor density in both the hypothalamus and the amygdala. In the hypothalamus, but not the amygdala, this increase was interrupted on day 14 by a decrease in 5-HT1A receptors, which we suggest may be of physiological significance in modifying the eventual pattern of adult agonistic activity. 5. The results suggest that the sexual dimorphism in 5-HT turnover is predominantly presynaptic, relating to altered synthesis and/or release, and is not of sufficient magnitude or duration to produce adaptive responses in postsynaptic 5-HT1A or 5-HT2A receptors.

Defensive behaviors in wild and laboratory (Swiss) mice: the mouse defense test battery.

The development of laboratory rodent models for elicitation and measurement of a range of defensive behaviors raises the question of the relationship between defense in these animals and those of their wild congeners. To evaluate this relationship for mice, defensive responses to an anesthetized rat were compared for fourth-generation laboratory-bred wild mice and Swiss CD-1 (Swiss-Webster derived) laboratory mice in a Mouse Defense Test Battery. Wild mice showed enhanced levels of both freezing and flight, fleeing from distant approach of the predator in several situations and fleeing more quickly than the Swiss mice. However, Swiss mice did flee upon contact with the rat and also showed levels of several other defensive behaviors (risk assessment, defensive threat, and attack) that were often reliably higher than those of the wild mice. However, when wild mice were prevented from fleeing, their levels of defensive threat and attack were as high as, or at very short prey-predator distances higher than, those of the Swiss mice. These findings suggest that flight and freezing are the major defensive behaviors reduced in Swiss mice and that these reductions allow the appearance of higher levels of additional defensive behaviors in the laboratory animals. However, although Swiss mice do show lower levels of flight and freezing, their patterns of defensive behavior are sufficiently similar to those of wild mice that they provide adequate subjects for research on the biologic bases of defensive behavior. A final experiment indicated that when wild mice are familiarized with a chamber providing a place of concealment, they flee directly to this chamber on presentation of a rat, indicating that flight is a targeted response and not simply an abrupt increase in forward locomotion. Over 10 rat presentation trials with a blocked chamber entrance, however, this response declines.

Interindividual variability in Swiss male mice: relationship between social factors, aggression, and anxiety.

In the present study we carried out a series of experiments in Swiss albino male mice to investigate a) the effects of previous social experience on the levels of anxiety in the elevated plus-maze (EPM) and b) whether the response of males in the EPM differs in relation to the different social status. In Experiment 1 we tested in the EPM male mice that received different social experience. Results showed that individually housing generally increased measures of anxiety in the EPM compared with the group-housing condition. Moreover, aggressive males, screened during dyadic encounters in a neutral cage, displayed the highest levels of anxiety relative to the other experimental conditions. In Experiment 2 male mice remained group-housed and were observed to record their social status. Results showed that those animals rated as socially dominant displayed a higher level of EPM anxiety relative to subordinates. From an ethological perspective our findings may be interpreted in terms of coping strategies, with aggressive/dominant animals typified by higher levels of risk assessment and open-arm avoidance than defensive/subordinate animals.

An evolutionary approach to behavioral pharmacology: using drugs to understand proximate and ultimate mechanisms of different forms of aggression in mice.

Psychoactive drugs (Fluprazine and Chlordiazepoxide--CDP) were used as probes to test both differences or similarities in neurochemical substrates (proximal causations) and adaptive significance (ultimate causations) of different forms of intraspecific aggression in wild mice and laboratory Swiss CD-1 counterparts. Fluprazine (1-5 mg/kg) inhibited maternal attack on female, but not on male intruders. Thus, phenotypically different attack behaviors (offence and defence respectively) which have different functions may be modulated by different neurochemical substrates. Intrasexual attack and infanticide which are phenotypically different, but share similar functions (i.e. competition for mates and resources) were equally inhibited by Fluprazine (2 mg/kg) both in males and females of wild and laboratory mice. This indicates that the neural substrates of these behaviors are related and similarly regulated in the two sexes. Fluprazine was used to test the prediction of the evolutionary model on fighting strategies in male-male asymmetric contests as far as fighting ability and resource value (mating and cohabitation with a female) are concerned. Fluprazine inhibited the intensity of fighting (i.e. more 'defensive' behavioral phenotype of attack) only in animals without previous positive fighting experience, suggesting that different behavioral strategies are based on different neurochemical modulation. Experience of attack also influenced the effects of CDP (2.5-5 mg/kg) in both lactating females and male resident mice. The reported proaggressive effects of benzodiazepines were observed only in animals with prior fighting experience in both cases. Thus the understanding of the effects of drugs on behavior demands consideration of the biological variability (e.g. genetic, previous experience and/or interindividual differences) and the adaptive significance of behavior in the experimental context. On this background ethopharmacology can be defined as an evolutionary approach to the study of a drugs effect on neurochemical mechanisms and functions of behavior.

Differential effects of chlordiazepoxide on aggressive behavior in male mice: the influence of social factors.

The present study examined the influence of prior social experience on the effects of chlordiazepoxide (CDP; 5.0, 10.0 and 20.0 mg/kg) on intrasexual aggression in male mice. Prior to drug testing, animals were either individually housed or screened in dyadic encounters in a neutral cage. This novel method yielded four experimental groups comprising animals with different social experiences and different aggressive/defensive characteristics: 1) individually-housed males (I): 2) aggressive males (A); 3) counter-attacking males (C), which actively responded to but did not initiate attack; and 4) defeated males (D). Twenty-four hours after screening, animals were treated with CDP and subjected to a resident-intruder test with untreated intruders. Results indicated that the lowest dose of CDP (5 mg/kg) increased aggressive behaviour but only in A males. At higher doses (10-20 mg/kg), CDP reduced attacks towards intruders in A, C and I, but not D, males. In A and C males, the antiaggressive action of CDP was associated with a prosocial effect (increased social investigation), whereas in I males, reduced aggression was associated with an increase in fear-related behaviours. As these differential effects of CDP on intermale aggression cannot be fully explained by differences in behavioural baselines, present data highlight the importance of experiential background as a powerful variable in determining behavioural responses to benzodiazepines. Present findings therefore suggest that an understanding of drug effects on social behaviour demands consideration of biological variability in phenotype.

Comparing different forms of male and female aggression in wild and laboratory mice: an ethopharmacological study.

The purpose of this study was to compare the effects of 2 mg/kg fluprazine (a serotonergic psychoactive drug with antiaggressive properties) on intrasexual attack, infanticide, and predation (on an insect larva) in males and females of wild and Swiss mice. The results showed that, in both stocks of mice, fluprazine significantly inhibited intrasexual and infanticidal attack in both sexes, but predatory attack was not altered by the drug treatment. Motivational and neural substrates underlying intrasexual attack and infanticide appear, thus, to be related to each other, and similarly modulated in both males and females. Conversely, predatory attack seems to be under a different neurohumoral control. The similar regulation of proximal mechanisms of aggressive behavior observed in wild and Swiss mice suggests a common neurobiology of aggression. For this reason, the outbred laboratory Swiss mice appear to be a reliable model for studies on causal and functional mechanisms of aggression.