Olfactory preference conditioning changes the reward value of reinforced and non-reinforced odors

International audienceOlfaction is determinant for the organization of rodent behavior. In a feeding context, rodents must quickly discriminate whether a nutrient can be ingested or whether it represents a potential danger to them. To understand the learning processes that support food choice, aversive olfactory learning and flavor appetitive learning have been extensively studied. In contrast, little is currently known about olfactory appetitive learning and its mechanisms. We designed a new paradigm to study conditioned olfactory preference in rats. After 8 days of exposure to a pair of odors (one paired with sucrose and the other with water), rats developed a strong and stable preference for the odor associated with the sucrose solution. A series of experiments were conducted to further analyze changes in reward value induced by this paradigm for both stimuli. As expected, the reward value of the reinforced odor changed positively. Interestingly, the reward value of the alternative odor decreased. This devaluation had an impact on further odor comparisons that the animal had to make. This result suggests that appetitive conditioning involving a comparison between two odors not only leads to a change in the reward value of the reinforced odor, but also induces a stable devaluation of the non-reinforced stimulus

Shank2 Mutant Mice Display Hyperactivity Insensitive to Methylphenidate and Reduced Flexibility in Social Motivation, but Normal Social Recognition

Mouse models of autism can be used to study evolutionarily conserved mechanisms underlying behavioral abnormalities in social communication and repetitive behaviors. SHANK genes code for synaptic scaffolding proteins at excitatory synapses and mutations in all SHANK genes have been associated with autism. Here, we present three behavioral aspects of the mutant mice deleted for exon 16 in Shank2. First, we treated Shank2 mutant mice with methylphenidate to rescue the hyperactivity. Our failure to do so suggests that the hyperactivity displayed by Shank2 mutant mice is not related to the one displayed by the typical mouse models of hyperactivity, and might be more closely related to manic-like behaviors. Second, by testing the effect of group housing and social isolation on social interest, we highlighted that Shank2 mutant mice lack the typical flexibility to modulate social interest, in comparison with wild-type littermates. Finally, we established a new protocol to test for social recognition in a social context. We used this protocol to show that Shank2 mutant mice were able to discriminate familiar and unknown conspecifics in free interactions. Altogether, these studies shed some light on specific aspects of the behavioral defects displayed by the Shank2 mouse model. Such information could be used to orient therapeutic strategies and to design more specific tests to characterize the complex behavior of mouse models of autism

Adult Male Mice Emit Context-Specific Ultrasonic Vocalizations That Are Modulated by Prior Isolation or Group Rearing Environment

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

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

Quartet of familiar males – 17q21.31 Del mouse strain – 2 WT + 2 Del/+ - M8

We monitored the individual and social behaviours of each quartet of mice over three days and nights in the Live Mouse Tracker system (LMT, plugin 931; de Chaumont et al. 2019 Nat. Biomed. Engin.). This system tracks individually mice living in a group over several days and nights and extracts automatically the number, total duration and mean duration of more than thirty behavioural events describing the posture of the mouse, the types of social contacts, the dynamic social approach and escapes and complex social groupings (see de Chaumont et al. 2019 Nat. Biomed. Engin.). In this system, the four mice (10-14 weeks of age; 2 WT mice and 2 Del/+ mice) from the same housing cage (housed together from weaning on) were left undisturbed for 71 hours in a large transparent Plexiglas cage (50 x 50 x 40 cm), with fresh bedding, a house (width: 100 mm, depth: 75 mm, height: 40 mm) in red Plexiglas, 6 dental cotton rolls as well as food and water ad libitum. Light/dark cycle and temperature conditions were similar to those of the housing room (12/12h light/dark, lights on at 07:00 AM, 100 lux when the lights were on). Each recording session started between 03:00 and 04:00 PM. At the end of the session, mice were placed back in their home cage and the LMT setup was cleaned with soap water and dried with paper towels. The upload includes the sqlite database from LMT (processed)

Quartet of familiar males – 17q21.31 Del mouse strain – 2 WT + 2 Del/+ - M5

We monitored the individual and social behaviours of each quartet of mice over three days and nights in the Live Mouse Tracker system (LMT, plugin 931; de Chaumont et al. 2019 Nat. Biomed. Engin.). This system tracks individually mice living in a group over several days and nights and extracts automatically the number, total duration and mean duration of more than thirty behavioural events describing the posture of the mouse, the types of social contacts, the dynamic social approach and escapes and complex social groupings (see de Chaumont et al. 2019 Nat. Biomed. Engin.). In this system, the four mice (10-14 weeks of age; 2 WT mice and 2 Del/+ mice) from the same housing cage (housed together from weaning on) were left undisturbed for 71 hours in a large transparent Plexiglas cage (50 x 50 x 40 cm), with fresh bedding, a house (width: 100 mm, depth: 75 mm, height: 40 mm) in red Plexiglas, 6 dental cotton rolls as well as food and water ad libitum. Light/dark cycle and temperature conditions were similar to those of the housing room (12/12h light/dark, lights on at 07:00 AM, 100 lux when the lights were on). Each recording session started between 03:00 and 04:00 PM. At the end of the session, mice were placed back in their home cage and the LMT setup was cleaned with soap water and dried with paper towels. The upload includes the sqlite database from LMT (processed)

Quartet of familiar males – 17q21.31 Del mouse strain – 2 WT + 2 Del/+ - M7

We monitored the individual and social behaviours of each quartet of mice over three days and nights in the Live Mouse Tracker system (LMT, plugin 931; de Chaumont et al. 2019 Nat. Biomed. Engin.). This system tracks individually mice living in a group over several days and nights and extracts automatically the number, total duration and mean duration of more than thirty behavioural events describing the posture of the mouse, the types of social contacts, the dynamic social approach and escapes and complex social groupings (see de Chaumont et al. 2019 Nat. Biomed. Engin.). In this system, the four mice (10-14 weeks of age; 2 WT mice and 2 Del/+ mice) from the same housing cage (housed together from weaning on) were left undisturbed for 71 hours in a large transparent Plexiglas cage (50 x 50 x 40 cm), with fresh bedding, a house (width: 100 mm, depth: 75 mm, height: 40 mm) in red Plexiglas, 6 dental cotton rolls as well as food and water ad libitum. Light/dark cycle and temperature conditions were similar to those of the housing room (12/12h light/dark, lights on at 07:00 AM, 100 lux when the lights were on). Each recording session started between 03:00 and 04:00 PM. At the end of the session, mice were placed back in their home cage and the LMT setup was cleaned with soap water and dried with paper towels. The upload includes the sqlite database from LMT (processed)

Quartet of familiar males – 17q21.31 Del mouse strain – 2 WT + 2 Del/+ - M3

We monitored the individual and social behaviours of each quartet of mice over three days and nights in the Live Mouse Tracker system (LMT, plugin 931; de Chaumont et al. 2019 Nat. Biomed. Engin.). This system tracks individually mice living in a group over several days and nights and extracts automatically the number, total duration and mean duration of more than thirty behavioural events describing the posture of the mouse, the types of social contacts, the dynamic social approach and escapes and complex social groupings (see de Chaumont et al. 2019 Nat. Biomed. Engin.). In this system, the four mice (10-14 weeks of age; 2 WT mice and 2 Del/+ mice) from the same housing cage (housed together from weaning on) were left undisturbed for 71 hours in a large transparent Plexiglas cage (50 x 50 x 40 cm), with fresh bedding, a house (width: 100 mm, depth: 75 mm, height: 40 mm) in red Plexiglas, 6 dental cotton rolls as well as food and water ad libitum. Light/dark cycle and temperature conditions were similar to those of the housing room (12/12h light/dark, lights on at 07:00 AM, 100 lux when the lights were on). Each recording session started between 03:00 and 04:00 PM. At the end of the session, mice were placed back in their home cage and the LMT setup was cleaned with soap water and dried with paper towels. The upload includes the sqlite database from LMT (processed)

Quartet of familiar males – 17q21.31 Del mouse strain – 2 WT + 2 Del/+ - M1

We monitored the individual and social behaviours of each quartet of mice over three days and nights in the Live Mouse Tracker system (LMT, plugin 931; de Chaumont et al. 2019 Nat. Biomed. Engin.). This system tracks individually mice living in a group over several days and nights and extracts automatically the number, total duration and mean duration of more than thirty behavioural events describing the posture of the mouse, the types of social contacts, the dynamic social approach and escapes and complex social groupings (see de Chaumont et al. 2019 Nat. Biomed. Engin.). In this system, the four mice (10-14 weeks of age; 2 WT mice and 2 Del/+ mice) from the same housing cage (housed together from weaning on) were left undisturbed for 71 hours in a large transparent Plexiglas cage (50 x 50 x 40 cm), with fresh bedding, a house (width: 100 mm, depth: 75 mm, height: 40 mm) in red Plexiglas, 6 dental cotton rolls as well as food and water ad libitum. Light/dark cycle and temperature conditions were similar to those of the housing room (12/12h light/dark, lights on at 07:00 AM, 100 lux when the lights were on). Each recording session started between 03:00 and 04:00 PM. At the end of the session, mice were placed back in their home cage and the LMT setup was cleaned with soap water and dried with paper towels. The upload includes the sqlite database from LMT (processed)

Der Einfluss von Umweltfaktoren auf die vokale Kommunikation bei Anubispavianen (Papio hamadryas anubis)

Bei nicht-menschlichen Primaten wurde vor allem beim Einsatz von vokalen Signalen eine Flexibilität nachgewiesen, im Gegensatz zur vokalen Produktion, die wesentlich starrer zu sein scheint. In der vorliegenden Arbeit werden zwei Sichtweisen eingenommen, um den Grad der Flexibilität beim Einsatz und der Struktur von Kontaktrufen von Pavianen -Grunzer (grunts), klare Beller (clear barks) und laute Rufe (loud calls)- zu untersuchen, wobei beim Einsatz die höchste Flexibilität erwartet wurde. Zum einen wurde, aus einer evolutiven Perspektive betrachtet, die Variabilität innerhalb und zwischen verschiedenen Paviantaxa untersucht. Hierbei wurden Tonaufnahmen und Verhaltensdaten, die von zwei in Nigeria lebenden Anubispaviangruppen (Papio hamadryas anubis) gesammelt wurden, mit den Daten von anderen Pavianpopulationen und -taxa verglichen. Zum anderen wurde der Grad der intraindividuellen Flexibilität beurteilt mit Schwerpunkt auf ökologische Faktoren. Dazu wurden in einem Review von Studien bei Froschlurchen, Vögeln und Säugern verschiedene Hypothesen über umweltbezogenen Schwankungen des vokalen Verhaltens getestet und das Habitat der untersuchten Paviane bezüglich seiner Struktur und akustischen Eigenschaften charakterisiert. Anschließend wurde die intraindividuelle Flexibilität als Antwort auf Habitatveränderungen untersucht, wobei die Daten vom vokalen Verhalten der nigerianischen Anubispaviane kombiniert wurden mit denen einer in Uganda lebenden Anubispaviangruppe. Zwischen den Anubispavianpopulationen und zwischen den Paviantaxa schwankte die Rufrate von Grunzern, klaren Bellern und lauten Rufen stark, während die Kontexte in denen die Rufe geäußert wurden und die akustische Struktur der Rufe nur geringe Unterschiede aufwiesen. Der Review von Studien bei Froschlurchen, Vögeln und Säugern zeigte, dass die umweltbezogenen Anpassungen des vokalen Verhaltens auf Art- oder Populationsniveau zum großen Teil mit den auf den Eigenschaften der Schallausbreitung basierenden Vorhersagen übereinstimmten, aber dass diese Anpassungen trotzdem nicht so weit verbreitet waren wie erwartet. Da der Review auch deutlich machte wie wichtig eine detaillierte Beschreibung der Umwelt ist, wurden das offene und geschlossene Habitat des Streifgebietes der untersuchten Anubispaviane genau charakterisiert. Die untersuchten Paviane passten ihre Grunzdauer an die Sichtbarkeitsbedingungen des Habitats an, sowohl in Nigeria als auch in Uganda. Die Grunzrate wurde dagegen nur von den Pavianen aus Uganda an die Sichtbedingungen angepasst. Allerdings beschränkten der Kontext in dem gerufen wurde und die Nähe zu Gruppenmitgliedern diese intraindividuelle Flexibilität. Bei Vokalisationen, die über lange Distanzen verwendet werden, tendierten die Paviane dazu, laute Rufe bei einem niedrigen Geräuschpegel der Umgebung zu äußern. Im Gegensatz dazu schien die Rufrate von klaren Bellern hauptsächlich von anderen Faktoren reguliert zu werden, wie einer erhöhten Prädationsgefahr oder der Erregung des rufenden Tieres. Insgesamt bestätigt die evolutive Herangehensweise, dass es eine größere Flexibilität beim Einsatz als bei der Struktur der Vokalisationen zwischen den Pavianpopulationen und -taxa gibt. Überraschenderweise trat die intraindividuelle Flexibilität als Antwort auf Habitatveränderungen systematisch bei der Produktion von Grunzern auf, aber nicht beim Einsatz von Rufen über kurze oder lange Distanzen. Diese intraindividuelle Plastizität könnte die Vorstufe eines gemeinsamen Vorfahren mit dem Menschen widerspiegeln, aus der sich die Fähigkeit der genauen Kontrolle der vokalen Produktion entwickelt hat, welche notwendig war für die Evolution der Sprache