eliciting-and-analyzing-male-mouse-ultrasonic-vocalization-usv-songs

Eliciting and Analyzing Male Mouse Ultrasonic Vocalization (USV) Songs

Mice produce ultrasonic vocalizations (USVs) in a variety of social contexts throughout development and adulthood. These USVs are used for mother-pup ...

Duke University

Howard Hughes Medical Institute

Social behavior is a defining mammalian feature that integrates emotional and motivational processes with external rewarding stimuli. It is thus an appropriate readout for complex behaviors, yet its neuronal and molecular bases remain poorly understood. In this study, we investigated the role of the mouse prefrontal area, particularly the involvement of β2-subunit nicotinic receptors (β2*-nAChRs) in a paradigm of social behavior with concurrent motivations. We previously observed that mice lacking β2*-nAChRs (β2(-/-)) display increased time in social contact and exaggerated approach movements toward the novel conspecific. Here, combining behavioral analysis, localized brain lesions, and lentiviral gene rescue, we found that c-Fos expression is specifically activated in the prelimbic (PrL) area of the prefrontal cortex (PFC) of mice exposed to a novel conspecific; lesions of the PrL area in wild-type mice produce the same social pattern as in β2(-/-) mice; and virally mediated reexpression of the β2-subunit in the PrL area of β2(-/-) mice rescues behavioral components in the social interaction task up to normal levels. Together, these data reveal that social interactions particularly mobilize the PrL area of the mouse PFC and that the presence of functional PrL β2*-nAChRs is necessary for this integrated behavior to emerge.

Prefrontal nicotinic receptors control novel social interaction between mice.

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Social interactions in mice are frequently analysed in genetically modified strains in order to get insight of disorders affecting social interactions such as autism spectrum disorders. Different types of social interactions have been described, mostly between females and pups, and between adult males and females. However, we recently showed that social interactions between adult males could also encompass cognitive and motivational features. During social interactions, rodents emit ultrasonic vocalizations (USVs), but it remains unknown if call types are differently used depending of the context and if they are correlated with motivational state. Here, we recorded the calls of adult C57BL/6J male mice in various behavioral conditions, such as social interaction, novelty exploration and restraint stress. We introduced a modulator for the motivational state by comparing males maintained in isolation and males maintained in groups before the experiments. Male mice uttered USVs in all social and non-social situations, and even in a stressful restraint context. They nevertheless emitted the most important number of calls with the largest diversity of call types in social interactions, particularly when showing a high motivation for social contact. For mice maintained in social isolation, the number of calls recorded was positively correlated with the duration of social contacts, and most calls were uttered during contacts between the two mice. This correlation was not observed in mice maintained in groups. These results open the way for a deeper understanding and characterization of acoustic signals associated with social interactions. They can also help evaluating the role of motivational states in the emission of acoustic signals.

Adult male mice emit context-specific ultrasonic vocalizations that are modulated by prior isolation or group rearing environment.

Les interactions sociales chez les souris sont fr&eacute;quemment analys&eacute;es dans les souches g&eacute;n&eacute;tiquement modifi&eacute;es afin d&#39;obtenir un aper&ccedil;u des probl&egrave;mes qui touchent les interactions sociales, comme les troubles du spectre autistique. Diff&eacute;rents types d&#39;interactions sociales ont &eacute;t&eacute; d&eacute;crits, principalement entre les femelles et les petits et entre femelles et m&acirc;les adultes. Cependant, nous avons montr&eacute; r&eacute;cemment que les interactions sociales entre m&acirc;les adultes pourraient englober &eacute;galement des fonctions cognitives et de motivationnels. Au cours des interactions sociales, rongeurs &eacute;mettent des vocalises ultrasonores (Cris), mais il reste inconnu si les types d&#39;appel sont utilis&eacute;s diff&eacute;remment en fonction du contexte et si elles sont corr&eacute;l&eacute;es avec l&#39;&eacute;tat de motivation. Ici, nous avons enregistr&eacute; les cris de souris m&acirc;les adultes de C57BL/6J dans diverses conditions comportementales, telles que l&#39;interaction sociale, exploration de la nouveaut&eacute; et le stress de la retenue. Nous avons introduit un modulateur pour l&#39;&eacute;tat de motivation en comparant les hommes maintenus en isolement et les m&acirc;les maintenus en groupes avant les exp&eacute;riences. Souris m&acirc;les ont prononc&eacute; des Cris dans toutes les situations sociales et non sociale et m&ecirc;me dans un contexte stressant retenue. Toutefois, ils ont &eacute;mise le nombre plus important d&#39;appels avec la plus grande diversit&eacute; des types d&#39;appel dans les interactions sociales, particuli&egrave;rement quand elle montre une forte motivation pour les contacts sociaux. Pour les souris maintenus dans l&#39;isolement social, le nombre d&#39;appels enregistr&eacute;s &eacute;tait positivement corr&eacute;l&eacute; avec la dur&eacute;e des contacts sociaux, et la plupart des appels ont &eacute;t&eacute; prononc&eacute;es au cours de contacts entre les deux souris. Cette corr&eacute;lation n&#39;a pas &eacute;t&eacute; observ&eacute;e chez les souris maintenus en groupes. Ces r&eacute;sultats ouvrent la voie &agrave; une compr&eacute;hension plus profonde et la caract&eacute;risation des signaux acoustiques associ&eacute;es aux interactions sociales. Ils peuvent aussi aider &agrave; &eacute;valuer le r&ocirc;le des &Eacute;tats motivationnels dans l&#39;&eacute;mission de signaux acoustiques.

Des souris m&acirc;les adultes &eacute;mettent contextuelle vocalisations ultrasoniques qui sont modul&eacute;es par isolement pr&eacute;alable ou le groupe environnement de l&#39;&eacute;levage.

Soziale Interaktionen bei M&auml;usen sind h&auml;ufig in gentechnisch ver&auml;nderten Sorten analysiert, um Einblick in Erkrankungen beeinflussen soziale Interaktionen wie Autismus-Spektrum-St&ouml;rungen. Verschiedene Arten von sozialen Interaktionen wurden beschrieben, meist zwischen Weibchen und Welpen sowie zwischen M&auml;nnchen und Weibchen. Jedoch haben wir vor kurzem gezeigt, dass soziale Interaktionen zwischen erwachsenen M&auml;nnern auch kognitive und Motivationale Merkmale umfassen k&ouml;nnte. W&auml;hrend soziale Interaktionen Nagetiere emittieren Ultraschall-Laute (USVs), aber es bleibt unklar, wenn Anruf Typen je nach Kontext unterschiedlich verwendet werden, und wenn sie mit motivationalen Zustand korreliert sind. Hier nahmen wir die Anrufe der Erwachsenen C57BL/6J m&auml;nnlichen M&auml;usen in verschiedenen Verhaltens Bedingungen, wie soziale Interaktion, Neuheit Exploration und Zur&uuml;ckhaltung Stress. Wir f&uuml;hrten Modulator f&uuml;r den motivationalen Zustand durch den Vergleich der M&auml;nner in Isolation und M&auml;nner in Gruppen vor den Experimenten verwaltet verwaltet. M&auml;nnliche M&auml;use ausgesprochen USVs in allen sozialen und nicht-sozialen Situationen und sogar in einem stressigen Zur&uuml;ckhaltung-Kontext. Sie dennoch ausgegeben die wichtigste Zahl der Anrufe mit der gr&ouml;&szlig;ten Vielfalt der Aufruf Typen in sozialen Interaktionen, vor allem, wenn eine hohe Motivation f&uuml;r sozialen Kontakt anzeigen. F&uuml;r M&auml;use, die in sozialer Isolation verwaltet die Anzahl der Anrufe aufgezeichnet wurde positiv korreliert mit der Dauer der sozialen Kontakte und die meisten Anrufe wurden ausgesprochen, w&auml;hrend Kontakte zwischen den zwei M&auml;usen. Dieser Zusammenhang wurde bei M&auml;usen, die in Gruppen verwaltet nicht beobachtet. Diese Ergebnisse &ouml;ffnen den Weg f&uuml;r ein tieferes Verst&auml;ndnis und Charakterisierung von akustischen Signalen Sozialinteraktionen zugeordnet. Sie k&ouml;nnen auch helfen, die Rolle der motivierenden Staaten in der Emission von akustische Signale auswerten.

Erwachsene m&auml;nnliche M&auml;use Strahlen kontextspezifische Ultraschall-Laute, die durch vorherige Isolation oder Gruppe Aufzucht Umwelt moduliert werden.

Le interazioni sociali nei topi sono frequentemente analizzate in ceppi geneticamente modificati al fine di ottenere la comprensione dei disturbi che interessano le interazioni sociali come disturbi dello spettro autistico. Sono stati descritti diversi tipi di interazioni sociali, soprattutto tra le femmine e i cuccioli e tra maschi e femmine adulti. Tuttavia, abbiamo recentemente dimostrato che le interazioni sociali tra maschi adulti potrebbero includere anche caratteristiche cognitive e motivazionali. Durante le interazioni sociali, roditori emettono vocalizzazioni ultrasoniche (USVs), ma rimane sconosciuto se tipi di chiamata sono utilizzati in modo diverso a seconda del contesto e se essi sono correlati con stato motivazionale. Qui, abbiamo registrato le chiamate dei topi maschi adulti C57BL/6J in diverse condizioni comportamentali, come interazione sociale, esplorazione di novit&agrave; e lo stress di moderazione. Abbiamo introdotto un modulatore per lo stato motivazionale confrontando i maschi mantenuti in isolamento e i maschi mantenuti in gruppi prima gli esperimenti. Topi maschi pronunciate USVs in tutte le situazioni sociali e non sociali e anche in un contesto di moderazione stressante. Essi tuttavia emessa il pi&ugrave; importante numero di chiamate con la pi&ugrave; grande diversit&agrave; dei tipi di chiamata nelle interazioni sociali, particolarmente quando mostrando una forte motivazione per il contatto sociale. Per topi mantenuti in isolamento sociale, il numero di chiamate registrate &egrave; stata positivamente correlato con la durata dei contatti sociali, e la maggior parte delle chiamate sono state pronunciate durante i contatti tra i due topi. Questa correlazione non &egrave; stata osservata nei topi mantenuti in gruppi. Questi risultati aprire la strada ad una pi&ugrave; profonda comprensione e caratterizzazione dei segnali acustici associati con le interazioni sociali. Possono anche contribuire a valutare il ruolo degli Stati motivazionali nell&#39;emissione di segnali acustici.

Topi maschi adulti emettono vocalizzazioni ultrasoniche contesto specifico che sono modulate dal previo isolamento o gruppo ambiente di allevamento.

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&#xC0DD;&#xC950;&#xC5D0;&#xC11C; &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD638; &#xC791;&#xC6A9;&#xC740; &#xC790;&#xC8FC; &#xC790;&#xD3D0;&#xC99D; &#xC2A4;&#xD399;&#xD2B8;&#xB7FC; &#xC7A5;&#xC560; &#xB4F1; &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD638; &#xC791;&#xC6A9;&#xC5D0; &#xC601;&#xD5A5;&#xC744; &#xBBF8;&#xCE58;&#xB294; &#xC7A5;&#xC560;&#xC5D0; &#xB300; &#xD55C; &#xD1B5;&#xCC30;&#xB825;&#xC744; &#xC5BB;&#xAE30; &#xC704;&#xD558;&#xC5EC; &#xC720;&#xC804;&#xC790; &#xBCC0;&#xD615;&#xB41C; &#xC885;&#xC790;&#xC5D0;&#xC11C; &#xBD84;&#xC11D; &#xB429;&#xB2C8;&#xB2E4;. &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD638; &#xC791;&#xC6A9;&#xC758; &#xC885;&#xB958;, &#xC131;&#xC778; &#xB0A8;&#xC131;&#xACFC; &#xC5EC;&#xC131; &#xADF8;&#xB9AC;&#xACE0; &#xC554;&#xCEF7;&#xACFC; &#xC0C8;&#xB07C;, &#xC0AC;&#xC774; &#xB300;&#xBD80;&#xBD84; &#xC124;&#xBA85; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, &#xC6B0;&#xB9AC;&#xB294; &#xCD5C;&#xADFC; &#xC131;&#xC778; &#xB0A8;&#xC131; &#xAC04;&#xC758; &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD638; &#xC791;&#xC6A9; &#xB610;&#xD55C; &#xC778;&#xC9C0; &#xD558; &#xACE0; &#xB3D9;&#xAE30; &#xBD80;&#xC5EC; &#xAE30;&#xB2A5;&#xC744; &#xD3EC;&#xAD04; &#xC218; &#xBCF4;&#xC600;&#xB2E4;. &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD638; &#xC791;&#xC6A9; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xC124;&#xCE58;&#xB958; &#xCD08;&#xC74C;&#xD30C; vocalizations (USVs)&#xC744; &#xBC29;&#xCD9C; &#xD558;&#xC9C0;&#xB9CC; &#xD638;&#xCD9C; &#xC885;&#xB958;&#xB294; &#xBB38;&#xB9E5;&#xC5D0; &#xB530;&#xB77C; &#xB2E4;&#xB974;&#xAC8C; &#xC0AC;&#xC6A9; &#xD558; &#xACE0; &#xB3D9;&#xAE30; &#xBD80;&#xC5EC; &#xC0C1;&#xD0DC;&#xC640; &#xC0C1;&#xAD00; &#xC54C; &#xC218; &#xC5C6;&#xB294; &#xC0C1;&#xD0DC;&#xB85C; &#xC720;&#xC9C0; &#xB429;&#xB2C8;&#xB2E4;. &#xC5EC;&#xAE30;&#xC5D0;, &#xC6B0;&#xB9AC;&#xB294; &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD638; &#xC791;&#xC6A9;, &#xC0C8;&#xB85C; &#xC6C0; &#xD0D0;&#xD5D8; &#xAD6C;&#xC18D; &#xC2A4;&#xD2B8;&#xB808;&#xC2A4; &#xB4F1; &#xB2E4;&#xC591; &#xD55C; &#xB3D9;&#xC791; &#xC870;&#xAC74;&#xC5D0;&#xC11C; &#xC131;&#xC778; C57BL/6J &#xB0A8;&#xC131; &#xC0DD;&#xC950;&#xC758; &#xD638;&#xCD9C;&#xC744; &#xAE30;&#xB85D; &#xD588;&#xB2E4;. &#xC6B0;&#xB9AC; &#xACE0;&#xB9BD;&#xACFC; &#xB0A8;&#xC131; &#xC2E4;&#xD5D8; &#xD558;&#xAE30; &#xC804;&#xC5D0; &#xADF8;&#xB8F9;&#xC5D0; &#xC720;&#xC9C0;&#xC5D0; &#xC720;&#xC9C0; &#xD558;&#xB294; &#xB0A8;&#xC131;&#xC744; &#xBE44;&#xAD50; &#xD558; &#xC5EC; &#xB3D9;&#xAE30; &#xBD80;&#xC5EC; &#xC0C1;&#xD0DC;&#xC5D0; &#xB300; &#xD55C; &#xBCC0;&#xC870;&#xAE30;&#xB97C; &#xC18C;&#xAC1C; &#xD588;&#xB2E4;. &#xBAA8;&#xB4E0; &#xC0AC;&#xD68C;&#xC801;&#xC774; &#xACE0; &#xBE44; &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD669; &#xBC0F; &#xC2A4;&#xD2B8;&#xB808;&#xC2A4; &#xC5B5;&#xC81C; &#xB9E5;&#xB77D; &#xC5D0;&#xC11C;&#xB3C4; &#xB0A8;&#xC131; &#xC0DD;&#xC950; USVs &#xAD6C;&#xC808;. &#xADF8;&#xB4E4;&#xC740; &#xADF8;&#xB7FC;&#xC5D0;&#xB3C4; &#xBD88;&#xAD6C; &#xD558; &#xACE0; &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD638; &#xC791;&#xC6A9;&#xC5D0;&#xC11C; &#xD1B5;&#xD654; &#xD615;&#xC2DD;&#xC758; &#xAC00;&#xC7A5; &#xD070; &#xB2E4;&#xC591;&#xC131; &#xD638;&#xCD9C;&#xC758; &#xAC00;&#xC7A5; &#xC911;&#xC694; &#xD55C; &#xC218;&#xB97C; &#xB0B4;&#xBCF4;&#xB0B8; &#xC0AC;&#xD68C;&#xC801; &#xC811;&#xCD09;&#xC5D0; &#xB300; &#xD55C; &#xB192;&#xC740; &#xB3D9;&#xAE30; &#xBD80;&#xC5EC;&#xB97C; &#xAC8C;&#xC7AC; &#xD558;&#xB294; &#xACBD;&#xC6B0;&#xC5D0; &#xD2B9;&#xD788;. &#xC0AC;&#xD68C;&#xC801; &#xACE0;&#xB9BD;&#xC5D0;&#xC11C; &#xC720;&#xC9C0; &#xAD00;&#xB9AC; &#xD558;&#xB294; &#xC950;&#xC5D0; &#xB300; &#xD55C; &#xD638;&#xCD9C; &#xAE30;&#xB85D; &#xC218;&#xB294; &#xC0C1;&#xAD00; &#xAD00;&#xACC4;&#xAC00; &#xAE0D;&#xC815;&#xC801;&#xC73C;&#xB85C; &#xC0AC;&#xD68C;&#xC801; &#xC5F0;&#xB77D;&#xCC98;&#xC758; &#xAE30;&#xAC04; &#xBC0F; &#xB450; &#xB9C8;&#xC6B0;&#xC2A4; &#xC0AC;&#xC774; &#xC811;&#xCD09; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xB300;&#xBD80;&#xBD84;&#xC758; &#xD1B5;&#xD654; &#xD588;&#xB2E4; &#xAD6C;&#xC808;. &#xC774; &#xC0C1;&#xAD00; &#xAD00;&#xACC4; &#xD558;&#xC9C0; &#xADF8;&#xB8F9;&#xC5D0;&#xC11C; &#xC720;&#xC9C0; &#xAD00;&#xB9AC; &#xD558;&#xB294; &#xC950;&#xC5D0;&#xC11C; &#xAD00;&#xCC30; &#xB418;&#xC5C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xACB0;&#xACFC; &#xB300; &#xD55C; &#xAE4A;&#xC740; &#xC774;&#xD574;&#xC640; &#xC0AC;&#xD68C;&#xC801; &#xC0C1;&#xD638; &#xC791;&#xC6A9;&#xC5D0; &#xC5F0;&#xAD00; &#xD558;&#xB294; &#xC74C;&#xD5A5; &#xC2E0;&#xD638;&#xC758; &#xD2B9;&#xC131; &#xBD84;&#xC11D; &#xBC29;&#xBC95;&#xC744; &#xC5FD;&#xB2C8;&#xB2E4;. &#xADF8;&#xB4E4;&#xC740; &#xB610;&#xD55C; &#xC74C;&#xD5A5; &#xC2E0;&#xD638; &#xBC29;&#xCD9C;&#xC5D0; &#xB3D9;&#xAE30; &#xBD80;&#xC5EC; &#xAD6D;&#xAC00;&#xC758; &#xC5ED;&#xD560;&#xC744; &#xD3C9;&#xAC00;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC131;&#xC778; &#xB0A8;&#xC131; &#xC950; &#xC774;&#xC804; &#xACA9;&#xB9AC; &#xB610;&#xB294; &#xADF8;&#xB8F9; &#xC591;&#xC721; &#xD658;&#xACBD;&#xC5D0; &#xC758;&#xD574; &#xBCC0;&#xC870; &#xB9DE;&#xB294; &#xCD08;&#xC74C;&#xD30C; vocalizations &#xBC29;&#xCD9C;.

Interacciones sociales en ratones se analizan con frecuencia en cepas gen&eacute;ticamente modificadas con el fin de tener una visi&oacute;n de los trastornos que afectan a las interacciones sociales, tales como trastornos del espectro autista. Se han descrito diferentes tipos de interacciones sociales, sobre todo entre las hembras y cr&iacute;as y entre las hembras y los machos adultos. Sin embargo, recientemente demostr&oacute; que las interacciones sociales entre machos adultos tambi&eacute;n podr&iacute;an abarcar las caracter&iacute;sticas cognitivas y motivacionales. Durante las interacciones sociales, roedores emiten vocalizaciones ultras&oacute;nicas (USVs), pero desconoce si los tipos de llamada se utilizan diferentemente dependiendo del contexto y se correlacionan con el estado motivacional. Aqu&iacute;, se registraron las llamadas de ratones machos adultos de C57BL/6J en diversas condiciones de comportamiento, como interacci&oacute;n social, la exploraci&oacute;n de la novedad y el estr&eacute;s de moderaci&oacute;n. Hemos introducido un modulador para el estado motivacional comparando los machos mantenidos en aislamiento y machos mantenidos en grupos antes de los experimentos. Ratones machos pronunci&oacute; USVs en todas las situaciones sociales y no social e incluso en un contexto de moderaci&oacute;n estresante. Sin embargo emitieron el n&uacute;mero m&aacute;s importante de llamadas con la mayor diversidad de tipos de llamada en las interacciones sociales, particularmente al mostrar una alta motivaci&oacute;n para el contacto social. Para los ratones mantenidos en aislamiento social, el n&uacute;mero de llamadas registradas se correlacion&oacute; positivamente con la duraci&oacute;n de los contactos sociales, y mayor&iacute;a de las llamadas fueron pronunciada durante los contactos entre los dos ratones. Esta correlaci&oacute;n no fue observada en ratones mantenidos en grupos. Estos resultados abren el camino para una m&aacute;s profunda comprensi&oacute;n y caracterizaci&oacute;n de se&ntilde;ales ac&uacute;sticas asociados con las interacciones sociales. Tambi&eacute;n pueden ayudar a evaluar el papel de los Estados motivacionales en la emisi&oacute;n de se&ntilde;ales ac&uacute;sticas.

Ratones machos adultos emiten vocalizaciones ultras&oacute;nicos contextos espec&iacute;ficos que son moduladas por aislamiento previo o grupo entorno de cr&iacute;a.

The study of social interactions in mice is used as a model for normal and pathological cognitive and emotional processes. But extracting comprehensive behavioral information from videos of interacting mice is still a challenge. We describe a computerized method and software, MiceProfiler, that uses geometrical primitives to model and track two mice without requiring any specific tagging. The program monitors a comprehensive repertoire of behavioral states and their temporal evolution, allowing the identification of key elements that trigger social contact. Using MiceProfiler we studied the role of neuronal nicotinic receptors in the establishment of social interactions and risk-prone postures. We found that the duration and type of social interactions with a conspecific evolves differently over time in mice lacking neuronal nicotinic receptors (Chrnb2-/-, here called β2(-/-)), compared to C57BL/6J mice, and identified a new type of coordinated posture, called back-to-back posture, that we rarely observed in β2(-/-) mice.

Computerized video analysis of social interactions in mice.

In social environments, choosing between multiple rewards is modulated by the uncertainty of the situation. Here, we compared how mice interact with a conspecific and how they use acoustic communication during this interaction in a three chambers task (no social threat was possible) and a Social Interaction Task, SIT (uncertain situation as two mice interact freely). We further manipulated the motivational state of the mice to see how they rank natural rewards such as social contact, food, and novelty seeking. We previously showed that beta2-subunit containing nicotinic receptors-β2(*)nAChRs- are required for establishing reward ranking between social interaction, novelty exploration, and food consumption in social situations with high uncertainty. Knockout mice for β2(*)nAChRs-β2(-/-)mice- exhibit profound impairment in making social flexible choices, as compared to control -WT- mice. Our current data shows that being confronted with a conspecific in a socially safe environment as compared to a more uncertain environment, drastically reduced communication between the two mice, and changed their way to deal with a social conspecific. Furthermore, we demonstrated for the first time, that β2(-/-) mice had the same motivational ranking than WT mice when placed in a socially safe environment. Therefore, β2(*)nAChRs are not necessary for integrating social information or social rewards per se, but are important for making choices, only in a socially uncertain environment. This seems particularly important in the context of Social Neuroscience, as numerous animal models are used to provide novel insights and to test promising novel treatments of human pathologies affecting social and communication processes, among which Autistic spectrum disorders and schizophrenia.

Making choice between competing rewards in uncertain vs. safe social environment: role of neuronal nicotinic receptors of acetylcholine.

In 2005, Holy and Guo advanced the idea that male mice produce ultrasonic vocalizations (USV) with some features similar to courtship songs of songbirds. Since then, studies showed that male mice emit USV songs in different contexts (sexual and other) and possess a multisyllabic repertoire. Debate still exists for and against plasticity in their vocalizations. But the use of a multisyllabic repertoire can increase potential flexibility and information, in how elements are organized and recombined, namely syntax. In many bird species, modulating song syntax has ethological relevance for sexual behavior and mate preferences. In this study we exposed adult male mice to different social contexts and developed a new approach of analyzing their USVs based on songbird syntax analysis. We found that male mice modify their syntax, including specific sequences, length of sequence, repertoire composition, and spectral features, according to stimulus and social context. Males emit longer and simpler syllables and sequences when singing to females, but more complex syllables and sequences in response to fresh female urine. Playback experiments show that the females prefer the complex songs over the simpler ones. We propose the complex songs are to lure females in, whereas the directed simpler sequences are used for direct courtship. These results suggest that although mice have a much more limited ability of song modification, they could still be used as animal models for understanding some vocal communication features that songbirds are used for.

Male mice song syntax depends on social contexts and influences female preferences.

Development of proficient spoken language skills is disrupted by mutations of the FOXP2 transcription factor. A heterozygous missense mutation in the KE family causes speech apraxia, involving difficulty producing words with complex learned sequences of syllables. Manipulations in songbirds have helped to elucidate the role of this gene in vocal learning, but findings in non-human mammals have been limited or inconclusive. Here, we performed a systematic study of ultrasonic vocalizations (USVs) of adult male mice carrying the KE family mutation. Using novel statistical tools, we found that Foxp2 heterozygous mice did not have detectable changes in USV syllable acoustic structure, but produced shorter sequences and did not shift to more complex syntax in social contexts where wildtype animals did. Heterozygous mice also displayed a shift in the position of their rudimentary laryngeal motor cortex (LMC) layer-5 neurons. Our findings indicate that although mouse USVs are mostly innate, the underlying contributions of FoxP2 to sequencing of vocalizations are conserved with humans.

A Foxp2 Mutation Implicated in Human Speech Deficits Alters Sequencing of Ultrasonic Vocalizations in Adult Male Mice.

Proposing a framework for the study of core functions is valuable for understanding how they are altered in multiple mental disorders involving prefrontal dysfunction, for understanding genetic influences and for testing therapeutic compounds. Social and communication disabilities are reported in several major psychiatric disorders, and social communication disorders also can occur independently. Being able to study social communication involving interactions and associated acoustic vocalizations in animal models is thus important. All rodents display extensive social behaviors, including interactions and acoustic vocalizations. It is therefore important to pinpoint potential genetic-related strain differences -and similarities- in social behavior and vocalization. One approach is to compare different mouse strains, and this may be useful in choosing which strains may be best suitable in modeling psychiatric disorders where social and communication deficits are core symptoms. We compared social behavior and ultrasonic acoustic vocalization profiles in males of four mouse strains (129S2/Sv, C57BL/6J, DBA/2, and CD-1) using a social interaction task that we previously showed to rely on prefrontal network activity. Our social interaction task promotes a high level of ultrasonic vocalization with both social and acoustic parameters, and further allows other measures of social behaviors. The duration of social contact, dominance and aggressiveness varied with the mouse strains. Only C57BL/6J mice showed no attacks, with social contact being highly affiliative, whereas others strains emitted aggressive attacks. C57BL/6J mice also exhibited a significantly higher rate of ultrasonic vocalizations (USV), especially during social interaction.

Article	Year
Prefrontal nicotinic receptors control novel social interaction between mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology\| PubMed ID: 21402717	2011
Adult male mice emit context-specific ultrasonic vocalizations that are modulated by prior isolation or group rearing environment. PloS one\| PubMed ID: 22238608	2012
Computerized video analysis of social interactions in mice. Nature methods\| PubMed ID: 22388289	2012
Making choice between competing rewards in uncertain vs. safe social environment: role of neuronal nicotinic receptors of acetylcholine. Frontiers in human neuroscience\| PubMed ID: 23986674	2013
Male mice song syntax depends on social contexts and influences female preferences. Frontiers in behavioral neuroscience\| PubMed ID: 25883559	2015
A Foxp2 Mutation Implicated in Human Speech Deficits Alters Sequencing of Ultrasonic Vocalizations in Adult Male Mice. Frontiers in behavioral neuroscience\| PubMed ID: 27812326	2016
Social behaviors and acoustic vocalizations in different strains of mice. Behavioural brain research\| PubMed ID: 27825934	2017

Jonathan Chabout

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