The prelimbic cortex but not the anterior cingulate cortex plays an important role in social recognition and social investigation in mice.

The prefrontal cortex (PFC) has been implicated in social cognitive functions and emotional behaviors in rodents. Each subregion (prelimbic cortex, PL; infralimbic cortex; and anterior cingulate cortex, ACC) of the PFC appears to play a different role in social and emotional behaviors. However, previous investigations have produced inconsistent data, and few previous studies directly compared the roles of the PFC subregions using the same experimental paradigm. Accordingly, in the present study, we examined the role of the PL and the ACC in short-term social recognition, social investigation, and anxiety-related behaviors in C57BL/6J mice. We subjected mice with a lesioned PL or ACC, as well as those in a sham control group, to tests of social recognition and social novelty where juvenile and adult male mice were used as social stimuli. In the social recognition test, the PL-lesioned mice exhibited habituation but not dishabituation regardless of whether they encountered juvenile or adult mice. In a subsequent social novelty test, they spent less time engaged in social investigation compared with the control mice when adult mice were used as social stimuli. These results suggest that PL lesions impaired both social recognition and social investigation. In contrast, ACC-lesioned mice did not exhibit impaired short-term social recognition or social investigation regardless of the social stimulus. Furthermore, PL lesions and ACC lesions did not affect anxiety-related behavior in the open field test or light-dark transition test. Our findings demonstrate that the PL but not the ACC plays an important role in social recognition and social investigation.

Testosterone interrupts binding of Neurexin and Neuroligin that are expressed in a highly socialized rodent, Octodon degus.

Octodon degus is said to be one of the most human-like rodents because of its improved cognitive function. Focusing on its high sociality, we cloned and characterized some sociality-related genes of degus, in order to establish degus as a highly socialized animal model in molecular biology. We cloned degus Neurexin and Neuroligin as sociality-related genes, which are genetically related to autism spectrum disorder in human. According to our results, amino acid sequences of Neurexin and Neuroligin expressed in degus brain, are highly conserved to that of human sequences. Most notably, degus Neuroligin4 is highly similar to human Neuroligin4X, which is one of the most important autism-related genes, whereas mouse Neuroligin4 is known to be poorly similar to human Neuroligin4X. Furthermore, our work also indicated that testosterone directly binds to degus Neurexin and intercepts intercellular Neurexin-Neuroligin binding. Moreover, it is of high interest that testosterone is another key molecule of the higher incidence of autism in male. These results indicated that degus has the potential for animal model of sociality, and furthermore may promote understanding toward the pathogenic mechanism of autism.

Auditory-induced visual illusions in rodents measured by spontaneous behavioural response.

When two brief sounds are presented with a short flash of light, we often perceive that the flash blinks twice. This phenomenon, called the "sound-induced flash illusion", has been investigated as an example of how humans finely integrate multisensory information, more specifically, the temporal content of perception. However, it is unclear whether nonhuman animals experience the illusion. Therefore, we investigated whether the Mongolian gerbil, a rodent with relatively good eyesight, experiences this illusion. The novel object recognition (NOR) paradigm was used to evaluate the gerbil's natural (i.e., untrained) capacity for multimodal integration. A light-emitting diode embedded within an object presented time-varying visual stimuli (different flashing patterns). The animals were first familiarised with repetitive single flashes. Then, various sound stimuli were introduced during test trials. An increase in exploration suggested that the animals perceived a flashing pattern differently only when the contradicting sound (double beeps) was presented simultaneously with a single flash. This result shows that the gerbil may experience the sound-induced flash illusion and indicates for the first time that rodents may have the capacity to integrate temporal content of perception in a sophisticated manner as do humans.

Effects of intraperitoneal and intracerebroventricular injections of oxytocin on social and emotional behaviors in pubertal male mice.

Oxytocin plays important roles in the social and emotional behaviors of mammals. In the present study, we examined the effects of intraperitoneal (IP) and intracerebroventricular (ICV) injections of oxytocin on these behaviors in pubertal male mice. Male C57BL/6J mice received IP injection of oxytocin (high-dose group: 1 mg/kg, low-dose group: 0.1 mg/kg), and ICV injection of oxytocin (0.5 µg/2 µL). Behavioral tests were conducted after administration of oxytocin at the age of 5-7 weeks. IP injection of high-dose oxytocin attenuated social investigation behavior toward both a novel and a cagemate mouse in the social preference test, and enhanced anxiogenic behavior and reduced general activity in the light-dark transition and elevated zero-maze tests. In contrast, ICV injection of oxytocin enhanced social investigation behavior toward both stimulus mice in the social preference test, and had no effects on anxiety-related behavior but increased general activity in the light-dark transition, elevated zero-maze, and open field tests. These results suggest that IP and ICV injections of oxytocin have significantly different effects on social and emotional behaviors in pubertal male mice. IP injection of oxytocin (1 mg/kg) appears to reduce social investigation behaviors and enhance anxiety-related behaviors, while ICV injection of oxytocin appears to enhance social investigation behaviors and general activity.

Influence of Pre-Weaning Social Isolation on Post-Weaning Emotion Tendency and Mother-Infant Interactions in Infant Octodon Degus.

Our previous research using Octodon degus (degus) revealed that preweaning social isolation negatively affected object exploratory behavior. However, it remains unknown how social isolation affects animal psychology and other behaviors. The present study examined the effects of neonatal social isolation on degu emotion and mother-infant interactions before and after weaning. Because degus have a complex social repertoire, we predicted that they would be sensitive to social isolation and show similarities with humans in their social interaction. Pups in the isolation group were separated from their family seven times for 30 min a day from 8 to 15 days post-birth. Pups in the nonisolation group were reared with their family. At 2, 3, 4, 5, and 6 weeks of age, pups underwent a zero-maze test to measure anxiety and a mother-infant interaction test to assess mother-infant attachment. Isolated pups showed more activity in the zero-maze test than nonisolated pups at 3 weeks of age. We found no significant effects of social isolation on mother-infant interactions. These results suggest that while neonatal social isolation might affect emotion during weaning, it does not influence mother-infant relationships.

[The role of the orbitofrontal cortex in delayed reinforcement choice in rats].

Previous studies have reported that lesions of the orbitofrontal cortex (OFC) in rats induce impulsive choices in delayed reinforcement tasks. However, some studies have suggested that the OFC is not related to impulsivity but instead to compulsivity. In this study, we investigated the effects of OFC lesions on choice in a T-maze. First, 14 rats were trained to discriminate spatially between a high-reward arm with a delay of 15 seconds and a low-reward arm without a delay. The high-reward arm contained 10 food pellets, whereas the low-reward arm contained only one pellet. In the presurgery test, all rats chose the high-reward arm in most trials. In the postsurgery test, both OFC lesioned (n = 7) and control (sham-lesioned and intact; n = 7) rats continued to choose the high-reward arm in most trials. Following the postsurgery test, the high- and low-reward arms were reversed. In the reversal test, OFC lesioned rats made significantly fewer high-reward choices than did control rats. These results indicate that OFC lesions induced compulsive choices rather than impulsive choices.

Hippocampus lesions induced deficits in social and spatial recognition in Octodon degus.

Previous studies of rodents reported that the hippocampus plays an important role in social behavior as well as spatial behavior. However, there are inconsistencies between reports of the effects of hippocampal lesions on social behavior. The present study sought to clarify the aspects of social behavior in which the hippocampus plays a role in the degu, Octodon degus, a social rodent. We examined the effects of hippocampal lesions on social behavior in the degu using familiar and novel partners. When placed in a familiar environment with a familiar partner after surgery, sham operation control (S.Cont) degus exhibited affinitive behavior longer compared with hippocampal lesioned (HPC) degus. In a novel environment, S.Cont degus exhibited longer aggressive behavior toward novel partners, and longer affinitive behavior with familiar partners compared with HPC degus. HPC degus did not show evidence of differentiation in social behavior, regardless of partner's novelty. The results of an anxiety test confirmed that these findings could not be attributed to changes in emotional state. We conducted an object-recognition test with the same subjects. HPC degus showed an impairment in spatial recognition but not object recognition. Taken together, these results suggest that the degu hippocampus plays an important role not only in spatial recognition but also social recognition. The changes in social behavior resulting from hippocampal lesions were interpreted as due to an impairment of social recognition rather than an impairment in novelty detection.

Pretraining does not ameliorate spatial learning deficits induced by intrahippocampal infusion of AP5.

Previous studies show discrepancies concerning the effects of pretraining on spatial learning deficits induced by blockade of the N-methyl-D-aspartate (NMDA) receptor. These inconsistencies might be attributed to the differences in the nature of the pretraining tasks and the method of blocking NMDA receptors. In the present study, the authors pretrained rats in a spatial water maze task. The authors then trained them with a novel spatial task in a novel environment under chronic blockade of hippocampal NMDA receptors by intrahippocampal infusion of 2-amino-5-phosphonopentanoic acid (AP5) using osmotic pumps. Although the rats had acquired the basic techniques needed to solve a water-maze spatial task during pretraining, those given high or low doses of AP5 showed acquisition deficits. As the spatial pretraining failed to ameliorate the acquisition deficits of a new task in a novel environment, it was suggested that NMDA receptors were necessary in forming spatial representations. Because neither dose of AP5 affected the performance of a spatial task in the retention phase, sensory motor disturbances could not have caused these deficits.

Dissociation of the roles of NMDA receptor and hippocampus in rats' spatial learning: the effects of environmental familiarity and task familiarity.

In this study, we compared the effects of MK-801 and hippocampal lesions on re-training of Morris water maze place task in familiar and novel environments in rats. In Experiment 1, rats were pre-trained with the place task. After acquiring the task, rats were re-trained with the same task in a familiar environment following MK-801 injection, and were then trained with the same task in a novel environment following MK-801 injection. In the familiar environment, MK-801 had no effect, but in the novel environment performance was impaired. In Experiment 2, after the place task training, the hippocampus was lesioned, and rats were re-trained with the same task in the familiar environment then retrained again in the novel environment. Rats showed severe impairment in both environments. These two experiments suggest different functions for NMDA receptors and the hippocampus. The results of Experiment 1 showed that NMDA receptors are not required for utilizing spatial representations but they play an important role in the construction of spatial representations. The results of Experiment 2 show that the hippocampus is necessary for both the utilization of spatial representations already formed and the formation of new spatial representations.

NMDA antagonist MK-801 does not interfere with the use of spatial representation in a familiar environment.

There is disagreement among researchers concerning whether glutamatergic N-methyl-D-aspartate (NMDA) receptors play a role in constructing spatial representations. Therefore, the authors reexamined the effects of the NMDA antagonist on a spatial discrimination task using rats in a water pool. The authors confirmed that MK-801 impaired acquisition of the spatial discrimination task (Experiment 1). When rats were pretrained before drug treatment, MK-801 induced learning deficits in the novel environment but not in the familiar environment (Experiment 2). Moreover, in a familiar environment, MK-801 did not impair spatial learning, even when the task was completely novel for the rats (Experiment 3). These results suggest that NMDA receptors play an important role in the construction of spatial representations but not in the use of them.

[Interactive effect of MK-801 and pre-training on spatial learning in rats].

In experiment 1, the effect of an NMDA receptor antagonist, MK-801, on the formation of the spatial representation was investigated. The administration of 0.1 mg/kg of MK-801 induced learning deficits in rats (n = 10) with the Morris watermaze task. However, when rats (n = 10) were pre-trained in the same task without drug treatment, and then trained in the same task in a different environment under the influence of the same amount of the drug, their performance was not impaired. The result suggests that rats treated with MK-801 can acquire a spatial representation of their environment, and that the impairment shown by the drug-treated rats without pre-training may be due to the impairment in the learning of the problem-solving strategy required for the watermaze place task. Experiment 2 examined this possibility. Rats (n = 10) were pre-trained with a visual cue discrimination task without drug treatment and then trained in the place task with MK-801 (0.1 mg/kg) treatment. They did not show impairment in the place task, indicating that rats treated with MK-801 can learn a new problem-solving strategy. Thus the learning deficits of MK-801-treated rats that have not been pre-trained do not seem to be due to impaired acquisition of the spatial representation or of the learning of strategy required to solve the watermaze place task.