Exposure to extremely low-frequency electromagnetic fields improves social recognition in male rats

The effect of exposure to low-frequency electromagnetic fields (ELF EMFs) on social recognition was studied. The test was based upon a comparison between two encounters of an adult rat and a conspecific juvenile, separated by an interexposure interval (IEI). The exposure to ELF EMF of 1 mT intensity during 2 h for 9 days increased the duration of short-term memory of adult male Wistar rats up to 300 min. These data indicate, for the first time, that ELF EMF improves social recognition memory in rats.     

Centrally injected arginine vasopressin (AVP) facilitates social memory in rats

'Memory' for a juvenile conspecific in male rats can be measured by variation in duration of investigation times when the same juvenile is presented at different intervals. Typically, exposure of an adult male rat to a juvenile results in transient investigatory activity that rapidly declines with repeated exposures at short interexposure intervals (30 min). Longer interexposure intervals (120 min) result in re-investigation with durations similar or greater than the original investigation. Arginine vasopressin (AVP) injected into adult male rats intracerebroventricularly in doses of 0.5-2.0 ng immediately after investigation of the juvenile decreased social investigation of the same juvenile at the long (120 min) interexposure interval. This decrease in investigatory time was similar to that observed after a 30-min interexposure interval in untreated animals. These results support the hypothesis that increasing the availability of AVP in the central nervous system can improve the consolidation of olfactory information and improve conspecific recognition in rats.     

Social memory in the rat: circadian variation and effect of circadian rhythm disruption

Disruption of circadian rhythm can impair long-term passive avoidance memory of rats and mice. The present study investigated whether disruption of circadian rhythm can also impair social memory of male rats. Social memory was assessed using the social discrimination test, in which a short-term olfactory memory is formed by social interaction with a juvenile rat during a learning trial. After an intertrial interval, a retrieval trial is performed, in which social memory is expressed as a decreased attention paid to the same juvenile as compared to a new juvenile. First, the social memory at four different time points across the light-dark cycle was measured with an intertrial interval of 10 or 25 min. There was no significant circadian variation of social memory across the light-dark cycle. Subsequently, the effect of a -6 or 12-h phase shift on social memory was studied. These phase shifts were previously found to impair long-term passive avoidance memory. However, no effect of either phase shift was observed in the social discrimination test. It is concluded that the disruption of circadian rhythm had no effect on the social memory of rats. Differences between short-term social memory and long-term passive avoidance memory are discussed in relation to their apparent differential susceptibility to the effects of circadian rhythm disruption.     

Effects of fluprazine hydrochloride on conspecific odor preferences in rats

The effect of Fluprazine Hydrochloride (DU 27716) on preference for conspecific male, estrous female and food odors was examined in male rats utilizing a two-compartment choice apparatus. Treatment with 8.0 mg/kg Fluprazine enhanced the preference of males for male odors but had no effect on preference for either estrous female or food odors. The drug-induced enhancement of male odor preference is consistent with the suggestion that Fluprazine interferes in some way with the processing of olfactory stimuli which normally precede offensive attack. The failure of the drug to alter the preference of males for estrous female odors suggests that the increased sniffing of estrous females noted during social testing may be secondary to other sources of conspecific stimulation or may reflect a highly transitory effect on olfactory processes. These results suggest that the suppressive effects of Fluprazine on intermale aggression and copulation are mediated by somewhat distinct mechanisms.     

Chemosensory cues from the lacrimal and preputial glands stimulate production of IP3 in the vomeronasal organ and aggression in male mice

The social and reproductive behaviors of most mammals are modulated by chemosensory cues. The perception of some of these cues is mediated by the vomeronasal organ, which is a cartilage-encased elongated organ associated with the vomer bone in the rostral nasal cavity. Several studies have shown that chemosensory cues are present in urine, seminal fluid or vaginal secretions but only a few studies have focused on exocrine glands as a source of chemosensory cues. Here we show that chemosensory cues present in two exocrine glands, i.e., the preputial gland located at the caudal region and the lacrimal gland located at the rostral region, are capable of stimulating aggression in male mice. We further show that these extracts can stimulate the production of inositol-(1,4,5)-trisphosphate in the vomeronasal organ.     

Chemoinvestigatory and sexual behavior of male guinea pigs following vomeronasal organ removal

The vomeronasal organs of male guinea pigs were removed (VNX; n=10) or males experienced sham surgery (Sham; n=10). Subsequently a battery of chemosensory tests of investigatory responsiveness to conspecific urine was conducted. Additionally, male subjects were paired with female conspecifics for short and long periods and social and sexual behaviors were monitored. VNX males exhibited a depression in urine investigation and this depression became more profound following repeated testing and/or the passage of time. By 6.3 months following surgery, investigatory responsiveness to urine was practically eliminated. Maintenance of responsiveness to urine odors may require reinforcing input through the accessory olfactory system. In contrast to these effects on responsiveness to odors, VNX and Sham males were indistinguishable in their social and sexual behavior. These data indicate that male guinea pigs without a VNO: (1) Exhibit a depression of investigation of urine odors which is time dependent and which may involve an extinction-like process; (2) continue to discriminate classes of urine (e.g., urine from male vs urine from female conspecifics); and (3) exhibit normal sexual behavior. The vomeronasal organ in the male domestic guinea pig is apparently critical for the maintenance of normal responsiveness to sex odors but, in its absence, other sensory systems are capable of maintaining normal sexual behavior under conditions of laboratory testing.     

Neonatal Exposure of Rats to Antidepressants Affects Behavioral Reactions to Novelty and Social Interactions in a Manner Analogous to Autistic Spectrum Disorders

We have demonstrated that neonatal exposure to selective serotonin reuptake inhibitors has lasting effects on behavior and serotonergic neurons in Long Evans rats. Hyperserotoninemia and altered sensory processing are reported in autistic spectrum disorders (ASD). We hypothesized that early life exposure to SSRIs alters sensory processing, disrupts responses to novelty, and impairs social interactions in a manner similar to that observed in ASD. Male and female Long‐Evans rat pups were administered citalopram, buproprion, fluoxetine, or saline from postnatal day (P) 8–21. Rats were tested for response to a novel tone before weaning (P25). Later, rats were tested 2× for response to a novel object (P39), and to a novel conspecific (P78, P101). In addition, rats were assessed for juvenile play behaviors (P32–P34) and later, we assessed sexual response to an estrus female in male rats (P153–184). Antidepressant exposure increased freezing after tone, diminished novel object exploration, and reduced conspecific interaction up to 3× compared to saline exposed rats. Juvenile play was profoundly reduced in antidepressant‐exposed males when compared to saline exposed groups. Exposure to the SSRIs, but not bupropion disrupted male sexual behaviors. Moreover, specific male responses to female proceptive behaviors were disrupted in SSRI, but not bupropion exposed rats. We conclude that neonatal exposure to antidepressants in rats results in sensory and social abnormalities that parallel many of those reported in ASD. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.     

Phenotypic characterization of spatial cognition and social behavior in mice with 'knockout' of the schizophrenia risk gene neuregulin 1

Neuregulin-1 (NRG1) has been identified as a candidate susceptibility gene for schizophrenia. In the present study the functional role of the NRG1 gene, as it relates to cognitive and social processes known to be disrupted in schizophrenia, was assessed in mice with heterozygous deletion of transmembrane (TM)-domain NRG1 in comparison with wildtypes (WT). Social affiliative behavior was assessed using the sociability and preference for social novelty paradigm, in terms of time spent in: (i) a chamber containing an unfamiliar conspecific vs. an empty chamber (sociability), or (ii) a chamber containing an unfamiliar conspecific vs. a chamber containing a familiar conspecific (preference for social novelty). Social dominance and aggressive behavior were examined in the resident-intruder paradigm. Spatial learning and memory were assessed using the Barnes maze paradigm, while spatial working memory was measured using the continuous variant of the spontaneous alternation task. Barnes maze data revealed intact spatial learning in NRG1 mutants, with elevated baseline latency to enter the escape hole in male NRG1 mutants reflecting an increase in activity level. Similarly, although a greater number of overall arm entries were found, spontaneous alternation was unaffected in NRG1 mice. Social affiliation data revealed NRG1 mutants to evidence a specific loss of WT preference for spending time with an unfamiliar as opposed to a familiar conspecific. This suggests that NRG1 mutants show a selective impairment in response to social novelty. While spatial learning and working memory processes appear intact, heterozygous deletion of TM-domain NRG1 was associated with disruption to social novelty behavior. These data inform at a novel phenotypic level on the functional role of this gene in the context of its association with risk for schizophrenia.     

The perirhinal-entorhinal cortex, but not the hippocampus, is critical for expression of individual recognition in the context of the Coolidge effect

The Coolidge effect is a phenomenon in which males show renewed sexual interest in a novel female following copulation to satiety with another female. In golden hamsters, this phenomenon depends on the ability to recognize conspecifics using chemosensory cues processed through the main olfactory system. Here we tested whether olfactory targets in the hippocampal system support this natural form of recognition memory. Male hamsters received ibotenic acid lesions of the perirhinal-entorhinal cortex (PR-ENT) or hippocampus (H) and were allowed to copulate to satiety with a female conspecific, then were presented with two anesthetized females, the familiar mate and an unfamiliar female that copulated with another male. Sham-operated and H-lesioned subjects preferentially investigated the novel female, indicating intact recognition of individual identity. By contrast, PR-ENT-lesioned males failed to discriminate familiar and novel females, and this deficit could not be attributed to abnormal copulatory behavior during mating. All subjects were able to detect and discriminate between female odors when presented in isolation during a habituation-discrimination test, indicating that behavioral deficits shown by PR-ENT males were not due to anosmia or a general investigatory deficit. Thus, the perirhinal-entorhinal cortex, but not the hippocampus, is critical for the recognition of familiar conspecifics in this naturalistic situation. This study reveals an essential role for the perirhinal-entorhinal cortex, but not the hippocampus, in a natural form of recognition memory within the social behavior of hamsters. The findings show a strikingly similar pattern to the effects of selective damage to the same brain regions on performance in standard recognition memory tasks by rats and monkeys. Therefore, the present data extend our understanding of the differential role of structures of the hippocampal memory system, showing continuity across species and between formal laboratory tests and the function of memory in natural social behavior.     

Development of selectivity for natural sounds in the songbird auditory forebrain

In adult songbirds, auditory neurons in the primary auditory forebrain region of field L and a secondary auditory forebrain region of caudal mesopallium (CM) are highly responsive to natural sounds, such as conspecific song. Because these nuclei are involved in sensory representations of songs, we investigated how their function changes during development. We recorded neural responses to conspecific and tutor song and acoustically matched synthetic sounds in field L and lateral CM (CLM) of urethane-anesthetized juvenile male zebra finches of approximately 35 days of age. At this age, juvenile songbirds are memorizing the songs of their adult tutors but do not yet sing mature song. They are also starting to recognize songs of individual conspecifics. Compared with adult auditory forebrain neurons, juvenile neurons in field L were on average less responsive to auditory stimuli and exhibited less selectivity for natural sounds compared with the synthetic sounds. This developmental effect was more pronounced in the secondary subregions of L1 and L3 than in the primary thalamo-recipient subregion L2 of field L. CLM showed adultlike selectivity for natural sounds. Also, we did not find any evidence of memory for the tutor song in either field L or CLM. We note that the neural development of selective responses to conspecific song in the secondary subregions of field L is correlated with the emergence of individual song preference around 35 days of age. Therefore we suggest that the emergence of natural sound selectivity in field L could be important for the behavioral development of song recognition.     

Ontogenetic interaction between social relationships and defensive burying behavior in the rat

The present experiments clarify sexual and social relationship factors related to the development of defensive burying behavior in rats. Rats were raised in isolation, or in a variety of pairs differing in sex, age or familiarity during the juvenile and post-juvenile period. In Experiment 1, decreased burying behavior was found in both male and female rats during the juvenile stage when they were reared in isolation, or with an adult female, or for males reared with a same-age female. In Experiment 2, female rats isolated during the juvenile stage who were reared after the juvenile stage with a same-sex, non-isolated rat, showed as much burying behavior as rats reared with a littermate; this was not found for male rats. When both male and female rats isolated during the juvenile stage were reared with each other after isolation, they maintained reduced burying behavior in adulthood. These sex differences in the effect of different social groupings are likely due to the differences in social relationships during the juvenile and after puberty, when social dominance relationships emerge in male rats. In Experiment 3, the effects of social dominance relationships on burying behavior were investigated in male rats. Subordination increased the freezing tendency as a passive defense, while social tension accompanied with rearing with an adult male produced decreased burying behavior as a proactive defense. These findings suggest that affiliative relationships involving playful contacts activate and maintain burying behavior, but familiarity is not a significant factor, while dominance relationships modulate the patterns of burying behavior.     

Chemosensory signals of competition increase the skin conductance response in humans

In vertebrates, chemosensory signals of competition are communicated between conspecifics, eliciting behavioral and physiological adaptations in the perceiving animal. The current study investigates, whether chemosensory signals of competition are also communicated between humans, and whether they elicit physiological changes in the perceiver. It is further investigated whether personality traits alter this physiological responding. Axillary sweat was collected from six male donors during a competition (badminton match) and a sport control condition (running). The donors' testosterone rose stronger during the competition as compared to the sport control condition. The chemosensory stimuli were presented to 18 (9 male) participants through a constant-flow olfactometer, while the skin conductance response (SCR) was measured. Results reveal that the SCR was larger in response to chemosensory signals collected during the competition condition as compared to those collected during the sport control condition. Furthermore, regression analyses showed, that higher scores on trait social anxiety were related to larger SCRs towards the chemosensory signals of competition. The current result suggests that chemosensory signals of competition can be communicated between humans, and that they elicit orienting in the perceiving individual. These data are consistent with current research, suggesting that high socially anxious individuals process threatening social information preferentially. The current results add to the growing body of research into human chemosensory communication of social information, and extend previous research on the chemosensory communication of anxiety.     

Vomeronasal and/or olfactory mediation of ultrasonic calling and scent marking by female golden hamsters.

The role of the olfactory and vomeronasal systems in mediating odor-stimulated ultrasonic calling, flank marking, and vaginal marking by female hamsters was investigated by selective lesions of either system. Removal of the vomeronasal organ resulted in reduced frequencies of ultrasonic calling by estrous and nonestrous females in response to conspecific odors but it had no influence on either scent marking behavior during the same tests. When tested immediately after separation from a male, ultrasonic calling was not reduced by vomeronasal removal, indicating that such surgery does not cause deficits in calling ability and that the vomeronasal organ specifically mediates odor-stimulated calling. Zinc sulfate treatment of the olfactory mucosa led to reduction in the frequency of ultrasonic calling, flank marking, and vaginal marking in response to conspecific odors. Females' ability to discover buried food was also impaired by this treatment. Thus, the stimulation of both scent marking behaviors due to the perception of conspecific odors appears to be mediated primarily by the olfactory system, whereas stimulation of ultrasonic calling is mediated by both olfactory and vomeronasal systems.     

Regulatory role of carotid nerve afferences upon the frequency and pattern of spontaneous gasp complexes

Spontaneous gasps were recorded in pentobarbitone-anesthetized adult cats. Mean interval between gasps in 11 cats with their buffer nerves intact was of 65 sec; it was significantly prolonged to 174 sec after unilateral carotid neurotomy and to 403 sec after bilateral carotid neurotomy. Additional sectioning of both aortic nerves in two cats led to a further increase of intervals between gasps. Inhibition of chemosensory activity during dopamine infusions also reduced the frequency of gasps. Recording of chemosensory impulses from one carotid nerve after unilateral carotid neurotomy, showed reduced discharge frequency or silencing immediately after the augmented inspiration. This effect probably mediated the reduced amplitude of the following series of ventilatory cycles. It is suggested that the peripheral chemosensory inflow adjusts the gain of the vagal inspiration-augmenting reflex.     

Lesions that functionally disconnect the anterior and posterodorsal sub-regions of the medial amygdala eliminate opposite-sex odor preference in male Syrian hamsters (Mesocricetus auratus)

In many rodent species, such as Syrian hamsters, reproductive behavior requires neural integration of chemosensory information and steroid hormone cues. The medial amygdala (MA) processes both of these signals through anatomically distinct sub-regions; the anterior region (MeA) receives substantial chemosensory input, but contains few steroid receptor-labeled neurons, whereas the posterodorsal region (MePD) receives less chemosensory input, but contains a dense population of steroid receptors. Importantly, these sub-regions have considerable reciprocal connections, and the goal of this experiment was therefore to determine whether interactions between MeA and MePD are required for male hamsters' preference to investigate female over male odors. To functionally disconnect MeA and MePD, males received unilateral lesions of MeA and MePD within opposite brain hemispheres. Control males received either unilateral lesions of MeA and MePD within the same hemisphere or sham surgery. Odor preferences were measured using a 3-choice apparatus, which simultaneously presented female, male and clean odor stimuli; all tests were done under conditions that either prevented or allowed contact with the odor sources. Under non-contact conditions, males with asymmetrical lesions investigated female and male odors equally, whereas males in both control groups preferred to investigate female odors. Under contact conditions, all groups investigated female odors longer than male odors, although males with asymmetrical lesions displayed decreased investigation of female odors compared to sham males. These data suggest that MeA–MePD interactions are critical for processing primarily the volatile components of social odors and highlight the importance of input from the main olfactory system (MOS) to these nuclei in the regulation of reproductive behavior. More broadly, these results support the role of the MA in integrating chemosensory and hormone information, a process that may underlie social odor processing in a variety of behavioral contexts.     

Anatomical connections between the anterior and posterodorsal sub-regions of the medial amygdala: integration of odor and hormone signals

In many rodent species, such as Syrian hamsters, reproductive behavior requires neural integration of chemosensory information and steroid hormone cues. The medial amygdala processes both of these signals through anatomically distinct sub-regions; the anterior region (MeA) receives substantial chemosensory input, but contains few steroid receptor-labeled neurons, whereas the posterodorsal region (MePD) receives less chemosensory input, but contains dense populations of androgen and estrogen receptors. Importantly, these sub-regions have considerable reciprocal connections, and previous studies in our laboratory have shown that functional interactions between MeA and MePD are required for the preference to investigate opposite-sex odors in male hamsters. We therefore hypothesized that chemosensory and hormone signals are conveyed directly between MeA and MePD. To test this hypothesis, we injected the retrograde tracer, cholera toxin B (CTB), into either MeA or MePD of male subjects and identified whether retrogradely labeled cells within MePD or MeA, respectively, expressed (1) Fos protein following exposure to female or male odors or (2) androgen receptors (AR). Approximately 36% of CTB-labeled cells within MeA (that project to MePD) also expressed Fos following exposure to either social odor, compared to the only 13% of CTB-labeled cells within MePD (that project to MeA) that also expressed odor-induced Fos. In contrast, 57% of CTB-labeled cells within MePD also contained AR, compared to the 28% of CTB-labeled cells within MeA that were double-labeled for AR/CTB. These results provide the first anatomical evidence that chemosensory and hormone cues are conveyed directly between MeA and MePD. Furthermore, these data suggest that chemosensory information is conveyed primarily from MeA to MePD, whereas hormone information is conveyed primarily from MePD to MeA. More broadly, the interactions between MeA and MePD may represent a basic mechanism by which the brain integrates information about social cues in the environment with hormonal indices of reproductive state.     

N-methyl-D-aspartate improved social recognition potency in rats

Activation of N-methyl-D-aspartate (NMDA) receptors is believed to play an important role in cognitive processes. In the present study we addressed the question of whether systematically administered NMDA can improve social recognition in adult male rats. We utilized the paradigm in which an adult animal is exposed to the same or a novel juvenile during two successive interactions. The adults given NMDA (10, 25 and 50 mg/kg, s.c.) immediately after the initial exposure to a juvenile exhibited significantly reduced social investigation during the second encounter with the same juvenile performed both 120 and 240 min later. Reduction in social investigation was not observed in saline treated animals as well as in those treated with both NMDA and saline but re-exposed to novel juveniles. These results indicate that NMDA improved social recognition potency of adult animals and prolonged retention of previously stored olfactory information.     

Perseveration of attention to conspecific odors and novel objects in castrated gerbils

Castrated male and female gerbils were tested for odor preference and for attention to conspecific odors and a novel object. Castrated gerbils housed with sham-operates preferred home odors, discriminated between two groups of male gerbils by olfactory cues, and perseverated in attention to odors of male gerbils and to a novel object. Similar perseveration to male conspecific odors was shown in gerbils given injections of L-DOPA (30 mg/kg). Combined treatment (castration and L-DOPA) resulted in additive effects on perseveration. This research challenges two general hypotheses of gonadal hormone function. The first, that changes in odor preference after castration are due to a loss in testicular androgen, is insufficient, because (1) female as well as male gerbils showed similar perseveration to odors, (2) there was a significant correlation between LH and duration of investigation of male conspecific odors, and (3) L-DOPA, the dopamine precurser, also caused perseveration to conspecific odors. The second, that gonadal hormones are responsible for persistence of attention, cannot be broadly generalized, because castration with resultant elevation of LH and regression of ventral glands resulted in perseveration of attention in male and female gerbils.     

Neonatal novelty exposure, dynamics of brain asymmetry, and social recognition memory

Brief and transient early-life stimulation via neonatal handling and neonatal novelty exposure can lead to differential changes within the right and left brains. In rats, these lateralized changes have been demonstrated behaviorally, neuroanatomically, and neurophysiologically. Recently, we found that neonatal novelty exposure can prolong the duration of social recognition memory from less than 2 hr to at least 24 hr among male rats reared in social isolation and that this enhancement is associated with an initial right-turn preference in a novel testing cage. In contrast to stable forms of asymmetry, such as handedness, we show that this turning asymmetry is dynamic-decreasing as the animal adjusts to the novel testing environment over a 2-day period. This change in turning asymmetry was found only among animals that experienced neonatal novelty exposure during the first 3 weeks of their lives. Furthermore, individual differences in short-term social recognition memory for a conspecific can be predicted by this change in functional asymmetry.     

Olfactory bulbectomy and play fighting in juvenile rats

To determine the influence on play fighting of inputs to the brain that arise in or course through the olfactory bulbs juvenile male and female rats were bilaterally bulbectomized at 23 or 24 days of age. The frequency of play fighting and play initiation was observed in tests conducted in the home cage. Bulbectomy did not affect the frequency of play fighting or play initiation by males, but slightly increased the frequency of play fighting without altering play initiation in females. Since peripheral anosmia has only modest effects on play fighting, neither the chemosensory nor the modulatory influences of the olfactory bulbs on limbic system activity appear to be especially important in the control of play by juvenile rats.