Dissociated features of social cognition altered in mouse models of schizophrenia: Focus on social dominance and acoustic communication

Faure, Alexis; Nosjean, Anne; Pittaras, Elsa; Duchêne, Adeline; Andrieux, Annie; Gory-Fauré, Sylvie; Charvériat, Mathieu; Granon, Sylvie

doi:10.1016/j.neuropharm.2018.09.009

Cited by 13 publications

(8 citation statements)

References 47 publications

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“… 70 ), were also recorded in a social environment allowing free interactions between adult male mice. Such a behavioral setting has been shown to favor the emission of acoustic communication in adult animals of same sex ( 71 , 72 ). USVs emitted were counted, and no significant difference was observed between TPC DKO mice and WT mice ( SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Adult male mice previously isolated for 3 wk were left alone to explore a novel arena (50 cm × 25 cm) containing clean bedding for 30 min before an unknown conspecific -same age, sex, and WT-genotype was gently introduced in the arena for a 8-min free social interaction during which USVs were recorded ( 72 ). As previously described in detail elsewhere ( 71 ), an ultrasound microphone placed above the arena allows the continuous recording of USVs while mice are having free and reciprocal social interactions.…”

Section: Methodsmentioning

confidence: 99%

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Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion

Martucci

Launay

Kawakami

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Oxytocin (OT) is a prominent regulator of many aspects of mammalian social behavior and stored in large dense-cored vesicles (LDCVs) in hypothalamic neurons. It is released in response to activity-dependent Ca 2+ influx, but is also dependent on Ca 2+ release from intracellular stores, which primes LDCVs for exocytosis. Despite its importance, critical aspects of the Ca 2+ -dependent mechanisms of its secretion remain to be identified. Here we show that lysosomes surround dendritic LDCVs, and that the direct activation of endolysosomal two-pore channels (TPCs) provides the critical Ca 2+ signals to prime OT release by increasing the releasable LDCV pool without directly stimulating exocytosis. We observed a dramatic reduction in plasma OT levels in TPC knockout mice, and impaired secretion of OT from the hypothalamus demonstrating the importance of priming of neuropeptide vesicles for activity-dependent release. Furthermore, we show that activation of type 1 metabotropic glutamate receptors sustains somatodendritic OT release by recruiting TPCs. The priming effect could be mimicked by a direct application of nicotinic acid adenine dinucleotide phosphate, the endogenous messenger regulating TPCs, or a selective TPC2 agonist, TPC2-A1-N, or blocked by the antagonist Ned-19. Mice lacking TPCs exhibit impaired maternal and social behavior, which is restored by direct OT administration. This study demonstrates an unexpected role for lysosomes and TPCs in controlling neuropeptide secretion, and in regulating social behavior.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion

Martucci

Launay

Kawakami

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…In this case, it is important to consider the difference between the models. Faure et al (2018) evaluated social communication using the ultrasonic vocalization test, whereas we evaluated it by the social olfactory test. Vocalization tests may have limitations in that they may not account for the recognition of odors from familiar and stranger mice (Yang et al , 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, we are the first to show that maternal treatment with APZ considerably prevented VPA-treated juvenile animals from exhibiting impaired cognitive social communication. Faure et al (2018) reported that APZ had no major impact on the social communication of schizophrenia induced by the NMDA receptor antagonist MK-801 in mice. In this case, it is important to consider the difference between the models.…”

Section: Discussionmentioning

confidence: 99%

Maternal treatment with aripiprazole prevents the development of a valproic acid-induced autism-like phenotype in juvenile male mice

Ferreira¹,

Gomes²,

Neves³

et al. 2023

Behavioural Pharmacology

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Autism spectrum disorder (ASD) describes a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and repetitive behaviors. Aripiprazole (APZ) is an atypical antipsychotic that can safeguard mice against autism-like behavior induced by valproic acid (VPA). In the present study, we examined the effects of maternal treatment with APZ (10 mg/kg) in juvenile mice prenatally exposed to VPA on neurodevelopmental behaviors, social interactions, communication, and working memory, as well as synaptophysin (SYP), synaptosomal-associated protein, 25 kDa (SNAP-25) and microtubule-associated protein 2 (MAP-2) expression in the medial prefrontal cortex (mPFC) and cell viability in the hippocampus. In addition, to evaluate possible APZ interference with the anticonvulsant properties of VPA on pentylenetetrazole (PTZ)-induced seizures were evaluated. Maternal treatment with APZ significantly prevented body weight loss, self-righting, eye-opening, social interactions, social communication, and working memory deficits in mice prenatally exposed to VPA. Additionally, the decrease in the SYP, SNAP-25, and MAP-2 expressions in the mPFC and cell death in the hippocampus was prevented by APZ. Furthermore, APZ (10 mg/kg) did not interfere with the anticonvulsant effect of VPA (15 mg/kg) in animals with PTZ-induced seizures. These findings indicate that maternal treatment with APZ in pregnant mice exposed to VPA protects animals against the ASD-like behavioral phenotype, and this effect may be related, at least in part, to synaptic plasticity and neuronal protection in the PFC and hippocampus. APZ may serve as an effective pharmacological therapeutic target against autistic behaviors in the VPA animal model of ASD, which should be further investigated to verify its clinical relevance.

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“…Analysis of rodent USVs is a foundational technique that underlies a diverse crosssection of mental health and addiction research [16][17][18][19][20][21][22][23][24][25][26][27][28]. However, this technique is currently underutilized because USV tabulation is time-intensive, manual, and costly-each two minutes of recorded rodent vocalizations can require up to an hour to hand-score depending upon the number of calls present.…”

Section: Introductionmentioning

confidence: 99%

Acoustilytix™: A Web-Based Automated Ultrasonic Vocalization Scoring Platform

et al. 2021

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Ultrasonic vocalizations (USVs) are known to reflect emotional processing, brain neurochemistry, and brain function. Collecting and processing USV data is manual, time-intensive, and costly, creating a significant bottleneck by limiting researchers’ ability to employ fully effective and nuanced experimental designs and serving as a barrier to entry for other researchers. In this report, we provide a snapshot of the current development and testing of Acoustilytix™, a web-based automated USV scoring tool. Acoustilytix implements machine learning methodology in the USV detection and classification process and is recording-environment-agnostic. We summarize the user features identified as desirable by USV researchers and how these were implemented. These include the ability to easily upload USV files, output a list of detected USVs with associated parameters in csv format, and the ability to manually verify or modify an automatically detected call. With no user intervention or tuning, Acoustilytix achieves 93% sensitivity (a measure of how accurately Acoustilytix detects true calls) and 73% precision (a measure of how accurately Acoustilytix avoids false positives) in call detection across four unique recording environments and was superior to the popular DeepSqueak algorithm (sensitivity = 88%; precision = 41%). Future work will include integration and implementation of machine-learning-based call type classification prediction that will recommend a call type to the user for each detected call. Call classification accuracy is currently in the 71–79% accuracy range, which will continue to improve as more USV files are scored by expert scorers, providing more training data for the classification model. We also describe a recently developed feature of Acoustilytix that offers a fast and effective way to train hand-scorers using automated learning principles without the need for an expert hand-scorer to be present and is built upon a foundation of learning science. The key is that trainees are given practice classifying hundreds of calls with immediate corrective feedback based on an expert’s USV classification. We showed that this approach is highly effective with inter-rater reliability (i.e., kappa statistics) between trainees and the expert ranging from 0.30–0.75 (average = 0.55) after only 1000–2000 calls of training. We conclude with a brief discussion of future improvements to the Acoustilytix platform.

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Dissociated features of social cognition altered in mouse models of schizophrenia: Focus on social dominance and acoustic communication

Cited by 13 publications

References 47 publications

Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion

Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion

Maternal treatment with aripiprazole prevents the development of a valproic acid-induced autism-like phenotype in juvenile male mice

Acoustilytix™: A Web-Based Automated Ultrasonic Vocalization Scoring Platform

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