Impairments in synapse development are thought to cause numerous psychiatric disorders. Autism susceptibility candidate 2 (AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals with AUTS2 mutations.

Rodents' ultrasonic vocalizations (USVs) provide useful information for assessing their social behaviors. Despite previous efforts in classifying subcategories of time-frequency patterns of USV syllables to study their functional relevance, methods for detecting vocal elements from continuously recorded data have remained sub-optimal. Here, we propose a novel procedure for detecting USV segments in continuous sound data containing background noise recorded during the observation of social behavior. The proposed procedure utilizes a stable version of the sound spectrogram and additional signal processing for better separation of vocal signals by reducing the variation of the background noise. Our procedure also provides precise time tracking of spectral peaks within each syllable. We demonstrated that this procedure can be applied to a variety of USVs obtained from several rodent species. Performance tests showed this method had greater accuracy in detecting USV syllables than conventional detection methods. OPEN ACCESSCitation: Tachibana RO, Kanno K, Okabe S, Kobayasi KI, Okanoya K (2020) USVSEG: A robust method for segmentation of ultrasonic vocalizations in rodents. PLoS ONE 15(2): e0228907. https://doi.org/10.

IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

Sexual behaviors are instinctually exhibited without prior training, but they are modulated by experience. One of the precopulatory behaviors in adult male mice, courtship ultrasonic vocalizations (USVs), has attracted considerable academic attention recently. Male mice emit ultrasounds as courtship behavior when encountering females. However, the modulatory effects of experience on USVs remain unclear. In the present study, we aimed to clarify the effects of sociosexual experience and aging on adult male vocalizations. First, we examined the effect of aging. The number of USVs decreased in an age-dependent manner. Following this, young adult male mice were co-housed for two weeks with normal female mice or ovariectomized (OVX) female mice, or housed without female mice, and the number of courtship USVs before and after co-housing were compared. In males housed with normal or OVX females, USVs increased significantly after co-housing. In contrast, males housed without females did not exhibit a significant increase of USVs. A facilitative effect of co-housing with female mice on vocalizations was also observed in aged males. In addition, females used as co-housing partners became pregnant, and the reproductive rate may be related to the vocal activity observed in the partnered males. These results indicate that sociosexual experience and aging affect vocalization activity, which may be related to courtship and/or reproductive function.

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Cataplexy is triggered by laughter in humans and palatable food in mice. To further evaluate mice’s cataplexy, we examined courtship behavior in orexin neuron-ablated mice (ORX-AB), one of the animal models of narcolepsy/cataplexy. Wild-type female mice were placed into the home cage of male ORX-AB and cataplexy-like behavior was observed along with ultrasonic vocalizations (USVs), also known as the “love song”. ORX-AB with a female encounter showed cataplexy-like behavior both during the dark and light periods, whereas ORX-AB with chocolate predominantly showed it during the dark period. During the light period observation, more than 85% of cataplexy-like bouts were preceded by USVs. A strong positive correlation was observed between the number of USVs and cataplexy-like bouts. Cataplexy-like behavior in narcoleptic mice is a good behavioral measure to study the brain mechanisms behind positive emotion because they can be induced by different kinds of positive stimuli, including chocolate and female courtship.

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Impairments in synapse development are thought to cause numerous psychiatric disorders.Autism susceptibility candidate 2 (AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals with AUTS2 mutations.