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Using high-throughput analysis methods, the present study sought to determine the impact of prenatal high-fat dietary manipulations on isolation-induced ultrasonic vocalization production in both male and female Fmr1mutants on postnatal day 9. Prior to breeding, male FVB/129 Fmr1 wildtype and female Fmr1 heterozygous breeding pairs were assigned to 1 of 3 diet conditions: standard lab chow, omega-3 fatty acid-enriched chow, and a diet controlling for the fat increase. Prenatal exposure to omega-3 fatty acids improved reductions in the number of calls produced by Fmr1heterozygotes females. Moreover, diminished spectral purity in the female Fmr1homozygous mouse was rescued by exposure to both high-fat diets, although these effects were not seen in the male Fmr1knockout. Prenatal dietary fat manipulation also influenced several other aspects of vocalization production, such as the number of calls produced and their fundamental frequency, aside from effects due to loss of Fmr1.Specifically, in males, regardless of genotype, prenatal exposure to high omega-3s increased the average fundamental frequency of calls. These data support the need for future preclinical and clinical work elucidating the full potential of prenatal high-fat diets as a novel therapeutic alternative forFragile X syndrome. [ABSTRACT FROM AUTHOR]

There is growing interest in the mechanisms for natural sensory learning in pro-social contexts. Studies using a maternal model of social behavior in the mouse have provided new insight into the auditory processing of behaviorally relevant pup vocalizations, which are used as communication signals to elicit pup retrieval behavior by adult females. Whether neural and behavioral plasticity in response to these vocalizations reflect auditory associative learning linking the sounds to pups, versus simply a change in maternal responsiveness to evolved vocal signals, remains an open question. Here we describe a T-maze paradigm to track auditory learning as we pair an initially neutral, non-ethological stimulus with delivery of a pup for retrieval, which is intrinsically reinforcing for rodents. • Training is rapid and completely appetitive. • Over a period of 7 × 50-minute daily training sessions, animals increasingly use the sound to guide their arm choice for pup retrieval, with an increase in performance from chance to an average of ~80% on day 7. • This pairing method establishes a newly-formed sensory association using a natural maternal behavioral response, and lays a solid foundation for studies into the neurochemical and circuit mechanisms that mediate auditory associative learning in natural social contexts.

Normal or dysfunctional sexual behavior seems to be an important indicator of health or disease. Many health disorders in male patients affect sexual activity by directly causing erectile dysfunction, affecting sexual motivation, or both. Clinical evidence indicates that many diseases strongly disrupt sexual motivation and sexual performance in patients with depression, addiction, diabetes mellitus and other metabolic disturbances with obesity and diet-related factors, kidney and liver failure, circadian rhythm disorders, sleep disturbances including obstructive sleep apnea syndrome, developmental and hormonal disorders, brain damages, cardiovascular diseases, and peripheral neuropathies. Preclinical studies of these conditions often require appropriate experimental paradigms, including animal models. Male sexual behavior and motivation have been intensively investigated over the last 80 years in animal rat model. Sexual motivation can be examined using such parameters as: anticipatory behavior and 50-kHz ultrasonic vocalizations reflecting the emotional state of rats, initiation of copulation, efficiency of copulation, or techniques of classical (pavlovian) and instrumental conditioning. In this review article, we analyze the behavioral parameters that describe the sexual motivation and sexual performance of male rats in the context of animal experimental models of human health disorders. Based on analysis of the parameters describing the heterogeneous and complex structure of sexual behavior in laboratory rodents, we propose an approach that is useful for delineating distinct mechanisms affecting sexual motivation and sexual performance in selected disease states and the efficacy of therapy in preclinical investigations.

Vocalization, a means of social communication, is prevalent among many species, including humans. Both rats and mice use ultrasonic vocalizations (USVs) in various social contexts and affective states. The motor cortex is hypothesized to be involved in precisely controlling USVs through connections with critical regions of the brain for vocalization, such as the periaqueductal gray matter (PAG). However, it is unclear how neurons in the motor cortex are modulated during USVs. Moreover, the relationship between USV modulation of neurons and anatomical connections from the motor cortex to PAG is also not clearly understood. In this study, we first characterized the activity patterns of neurons in the primary and secondary motor cortices during emission of USVs in rats using large-scale electrophysiological recordings. We also examined the axonal projection of the motor cortex to PAG using retrograde labeling and identified two clusters of PAG-projecting neurons in the anterior and posterior parts of the motor cortex. The neural activity patterns around the emission of USVs differed between the anterior and posterior regions, which were divided based on the distribution of PAG-projecting neurons in the motor cortex. Furthermore, using optogenetic tagging, we recorded the USV modulation of PAG-projecting neurons in the posterior part of the motor cortex and found that they showed predominantly sustained excitatory responses during USVs. These results contribute to our understanding of the involvement of the motor cortex in the generation of USV at the neuronal and circuit levels., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Sharif et al.)

Drug addiction is thought to be driven by negative reinforcement, and it is thought that a shift from positive affect upon initial exposure to negative affect after chronic exposure to a drug is responsible for maintaining self-administration (SA) in addicted individuals. This can be modeled in rats by analyzing ultrasonic vocalizations (USVs), a type of intraspecies communication indicative of affective state based on the frequency of the emission: calls in the 22 kHz range indicate negative affect, whereas calls in the 50 kHz range indicate positive affect. We employed a voluntary chronic, long-access model of fentanyl SA to analyze affective changes in the response to chronic fentanyl exposure. Male Sprague-Dawley rats self-administered either fentanyl (N = 7) or saline (N = 6) for 30 consecutive days and USVs were recorded at four different time points: the day before the first SA session (PRE), the first day of SA (T01), the last day of SA (T30), and the first day of abstinence (ABS). At T01, the ratio of 50 to 22 kHz calls was similar between the fentanyl and saline groups, but at T30, the ratio differed between groups, with the fentanyl group showing significantly fewer 50 kHz calls and more 22 kHz calls relative to saline animals. These results indicate a shift toward a negative affect during drug use after chronic exposure to fentanyl and support negative reinforcement as a main driving factor of opioid addiction.

Rats emit a variety of calls in the 40–80 kHz range (50 kHz calls). While these calls are generally associated with positive affect, it is unclear whether certain calls might be used selectively in certain contexts. To examine this, we looked at ultrasonic calls in 30–40 day old male rats during the expectation of either play or food, both of which are reinforcing. Behavior and vocalizations were recorded while rats were in a test chamber awaiting the arrival of a play partner or food over seven days of testing. Control groups were included for the non-specific effects of food deprivation and social isolation. Play reward led to an increase in 50 kHz vocalizations, generally, with specific increases in trill and “trill with jump” calls not seen in other groups. Expectation of food reward did not lead to a significant increase in vocalizations of any type, perhaps due to the young age of our study group. Further, rats that were food deprived for the food expectation study showed markedly lower calls overall and had a different profile of call types compared to rats that were socially isolated. Taken together, the results suggest that trill-associated calls may be used selectively when rats are socially isolated and/or expecting a social encounter.

Delivery is a complex biological process involving hormonal and mechanical stimuli that together condition the survival and development of the fetus out of the womb. Accordingly, changes in the time or way of being born are associated with an alteration of fundamental biological functions and hypothesized to promote the emergence of neurodevelopmental disorders. Hence, the steadily rise in preterm birth and cesarean section (CS) delivery rates over the past years has become a worldwide health concern. In our previous work, we reported that even though no long-term autistic-like deficits were observed, mice born preterm by CS presented early transient neuronal and communicative defects. However, understanding if these alterations were due to an early birth combined with CS delivery, or if prematurity solely could lead to a similar outcome remained to be evaluated. Using mice born either at term or preterm by vaginal or CS delivery, we assessed early life ultrasonic vocalizations and the onset of eye opening. We report that alterations in communicative behaviors are finely attuned and specifically affected either by preterm birth or by the association between CS delivery and preterm birth in mice, while delayed onset of eye opening is due to prematurity. Moreover, our work further underlies a gender-dependent vulnerability to changes in the time and/or way of being born with distinct outcomes observed in males and females. Thus, our results shed light on the intricacy of birth alterations and might further explain the disparities reported in epidemiological studies. [ABSTRACT FROM AUTHOR]

Adolescents are highly motivated to engage in social interactions, and researchers have hypothesized that positive social relationships during adolescence can have long term, beneficial effects on stress reactivity and mental well‐being. Studies of laboratory rodents provide the opportunity to investigate the relationship between early social experiences and later behavioral and physiological responses to stressors. In this study, female Lister‐hooded rats (N = 12 per group) were either (a) provided with short, daily encounters (10 min/day) with a novel partner during mid‐adolescence (postnatal day 34–45; "social experience," SE, subjects) or (b) underwent the same protocol with a familiar cagemate during mid‐adolescence ("control experience," CE, subjects), or (c) were left undisturbed in the home cage (non‐handled "control," C, subjects). When tested in adulthood, the groups did not differ in behavioral responses to novel environments (elevated plus maze, open field, and light‐dark box) or in behavioral and physiological (urinary corticosterone) responses to novel social partners. However, SE females emitted significantly more 50 kHz ultrasonic vocalizations than control subjects both before and after social separation from a familiar social partner, which is consistent with previous findings in male rats. Thus, enhanced adolescent social experience appears to have long‐term effects on vocal communication and could potentially modulate adult social relationships. [ABSTRACT FROM AUTHOR]

Normal or dysfunctional sexual behavior seems to be an important indicator of health or disease. Many health disorders in male patients affect sexual activity by directly causing erectile dysfunction, affecting sexual motivation, or both. Clinical evidence indicates that many diseases strongly disrupt sexual motivation and sexual performance in patients with depression, addiction, diabetes mellitus and other metabolic disturbances with obesity and diet-related factors, kidney and liver failure, circadian rhythm disorders, sleep disturbances including obstructive sleep apnea syndrome, developmental and hormonal disorders, brain damages, cardiovascular diseases, and peripheral neuropathies. Preclinical studies of these conditions often require appropriate experimental paradigms, including animal models. Male sexual behavior and motivation have been intensively investigated over the last 80 years in animal rat model. Sexual motivation can be examined using such parameters as: anticipatory behavior and 50-kHz ultrasonic vocalizations reflecting the emotional state of rats, initiation of copulation, efficiency of copulation, or techniques of classical (pavlovian) and instrumental conditioning. In this review article, we analyze the behavioral parameters that describe the sexual motivation and sexual performance of male rats in the context of animal experimental models of human health disorders. Based on analysis of the parameters describing the heterogeneous and complex structure of sexual behavior in laboratory rodents, we propose an approach that is useful for delineating distinct mechanisms affecting sexual motivation and sexual performance in selected disease states and the efficacy of therapy in preclinical investigations. [ABSTRACT FROM AUTHOR]

Sickness behavior (SB) is considered part of the adaptive behavioral and neuroimmune changes that occur in response to inflammatory processes. However, SB is a motivational state modulated by the environmental context. The objective of this study was to evaluate if selenium could ameliorate symptoms of SB and if stress would affect these responses. We induced SB in rats using lipopolysaccharide (LPS). We choose selenium based on our findings of LPS-exposure decreasing selenium levels in rats. We exposed these rats to a psychogenic stress and studied motivational modulation paradigms, such as cure of the organism, preservation of the species, and fight or flight. We studied ultrasonic vocalizations, open-field behaviors, body weight, and IL-1 beta and IFN-gamma serum levels. LPS-induced SB was evidenced by decreased motor/exploratory activity and increased proinflammatory mediators' levels. Selenium treatment did not exert beneficial effects on SB, revealing that probably the selenium deficiency was not related to SB. When analyzed with the stress paradigm, the behavior of rats was differentially affected. LPS did not affect behavior in the presence of stress. SB was abrogated during stressor events to prioritize survival behaviors, such as fight-or-flight. Contrarily, the association of LPS, selenium, and stress induced SB even during stressor events, revealing that this combination induced a cumulative toxic effect. [ABSTRACT FROM AUTHOR]

Division of labour allows group-living species to efficiently complete tasks while minimizing resource expenditure. This generally involves task allocation between individuals. In territorial defence and parental care specifically, division of labour can be completed using different strategies, often involving one or more individuals defending the territory while others care for offspring. Little is known, however, about division of labour by monogamous and biparental mammals. We investigated labour division strategies across territorial defence and pup retrievals by monogamous, biparental, territorial California mice along with the role of vocal communication in coordinating these behaviours. Male and female pair-bonded California mice display aggression towards same-sex intruders and retrieve pups while alone, but how pairs complete these tasks while together remains unknown. We found that California mouse pairs used one of two strategies during territorial defence: (1) joint defence or (2) divided defence. Overall, these strategies were not altered by the intruder sex or the birth of pups. However, postpartum individuals spent more time alone in the nest and pairs spent less time together investigating intruders. Pup retrievals, conversely, followed a sex-specific strategy where mothers retrieved pups in 89% of pairs while males retrieved pups in 11% of pairs. This study shows for the first time that a monogamous and biparental rodent uses different strategies to divide labour during vital tasks of territorial defence and pup retrieval. Moreover, we found that vocal communication via sustained vocalizations were predictive of aggressive behaviour but not retrieval behaviour, indicating that vocalizations may only play a role in coordinating specific behaviours. Importantly, these strategies were task dependent and robust across intruder sex and parental status, providing a framework for better understanding division of labour in mammals. • Pairs defended territories across contexts using a joint or divided defence strategy. • There was a sex difference in pup retrievals such that females predominantly retrieved. • Male sustained vocalizations predicted defence behaviour but not retrieval behaviour. [ABSTRACT FROM AUTHOR]

Medications that enhance dopaminergic neurotransmission can be useful in the pharmacotherapy of posttraumatic stress disorder (PTSD), which manifests as fearful memory retrieval, anxiety and depression. We examined the effects of subchronic (15 days) treatment with select dopaminergic medications, including bromocriptine, modafinil, dihydrexidine, rotigotine and pramipexole, in a mouse model of PTSD induced by single prolonged stress (mSPS). The potential antidepressant-like and anxiolytic effects of the medications were measured by the forced swim test (FST) and the elevated plus maze (EPM) test, respectively. In addition, we studied the effects of these medications on memory retrieval in an auditory fear conditioning (FC) test, on ultrasonic vocalizations (USVs) induced by restraint stress, and on spontaneous locomotor activity (SLA). We report that a single exposure to a severe and complex set of stressors several days before testing increased immobility time in the FST and freezing in the FC paradigm and reduced the time spent in the open arms of the EPM. The stressed mice also displayed increased USVs, especially the short type. While none of the tested dopamine-mimetics exhibited anxiolytic-like effects, rotigotine produced antidepressant-like activity specifically in the mSPS-exposed animals. Moreover, both rotigotine and pramipexole shortened the duration of freezing in the fear conditioning test, but only in the mSPS-exposed mice. This study supports the hypothesis that the activation of dopaminergic D2/D3 receptors may be a promising pharmacotherapy for PTSD. • SPS in mice (mSPS) mimics PTSD-like symptoms. • Dopamine D2/D3 receptor agonists attenuate PTSD-like symptoms in mice. • Rotigotine exhibits antidepressant-like effects in mSPS-exposed mice. • Pramipexole and rotigotine inhibit conditioned fear in mSPS-exposed mice. [ABSTRACT FROM AUTHOR]

• Multi-hit early adversity affects sociability in males and anxiety in females. • Early adversity differentially alters gut microbiota according to sex. • Early adversity elicits sex-specific transcriptome changes in the prefrontal cortex. • Behavioral data correlate with prefrontal cortex gene expression and gut microbiota. The accumulation of adverse events in utero and during childhood differentially increases the vulnerability to psychiatric diseases in men and women. Gut microbiota is highly sensitive to the early environment and has been recently hypothesized to affect brain development. However, the impact of early-life adversity on gut microbiota, notably with regards to sex differences, remains to be explored. We examined the effects of multifactorial early-life adversity on behavior and microbiota composition in C3H/HeN mice of both sexes exposed to a combination of maternal immune activation (lipopolysaccharide injection on embryonic day 17, 120 µg/kg, i.p.), maternal separation (3hr per day from postnatal day (PND)2 to PND14) and maternal unpredictable chronic mild stress. At adulthood, offspring exposed to multi-hit early adversity showed sex-specific behavioral phenotypes with males exhibiting deficits in social behavior and females showing increased anxiety in the elevated plus maze and increased compulsive behavior in the marble burying test. Early adversity also differentially regulated gene expression in the medial prefrontal cortex (mPFC) according to sex. Interestingly, several genes such as Arc , Btg2 , Fosb , Egr4 or Klf2 were oppositely regulated by early adversity in males versus females. Finally, 16S-based microbiota profiling revealed sex-dependent gut dysbiosis. In males, abundance of taxa belonging to Lachnospiraceae and Porphyromonadaceae families or other unclassified Firmicutes, but also Bacteroides , Lactobacillus and Alloprevotella genera was regulated by early adversity. In females, the effects of early adversity were limited and mainly restricted to Lactobacillus and Mucispirillum genera. Our work reveals marked sex differences in a multifactorial model of early-life adversity, both on emotional behaviors and gut microbiota, suggesting that sex should systematically be considered in preclinical studies both in neurogastroenterology and psychiatric research. [ABSTRACT FROM AUTHOR]

Abstract The risk gene CACNA1C is strongly implicated in the etiology of all major psychiatric disorders, such as depressive disorder, bipolar disorder, autism spectrum disorder, and schizophrenia. These disorders feature high levels of comorbidity and share an overlap of symptoms; in particular, deficits in social functioning are common. Intriguingly, sex-dependent effects of CACNA1C single nucleotide polymorphisms on prevalence, health outcomes, and psychological traits have been reported, typically suggesting that women are more affected by CACNA1C mutations than men. In rodents, genetic modifications specifically targeting Cacna1c have repeatedly been linked to deficits in social behavior in male mice and rats but many studies neglect the sex-dependent effects observed in humans. Our study focused on the role of Cacna1c in regulating social behavior and communication in adult female rats. We compared social and non-social behavior together with concomitant emission of pro-social 50-kHz ultrasonic vocalizations (USV) associated with positive affect in constitutive heterozygous (Cacna1c+/−) rats to wildtype (Cacna1c+/+) littermate controls. Our results indicate that partial Cacna1c depletion leads to strongly reduced emission of 50-kHz USV and mild social deficits during female direct reciprocal social interaction. Detailed temporal analyses revealed most prominent reductions of 50-kHz USV during non-social behavior, suggesting that reduced positive affect occurs in a social context in Cacna1c+/− rats but is not specifically linked to social behavior. Finally, we observed increased self-grooming behavior in Cacna1c+/− rats, consistent with an autism-like phenotype. Our findings in rats thus support a role of Cacna1c in regulating behavioral phenotypes with relevance for several neuropsychiatric disorders. Highlights • The CACNA1C gene is involved in the etiology of neuropsychiatric disorders. • Women seem to be more affected by CACNA1C alterations than men. • In rodents, mutations of Cacna1c have been linked to reduced sociability. • In female rats, social deficits arise following partial Cacna1c depletion. • In particular, the emission of 50-kHz ultrasonic vocalizations is strongly reduced. [ABSTRACT FROM AUTHOR]

• Selectively-bred high- and low-responder rats differed in affect in early life. • High- and low-responder rats showed different opioid gene expression. • Neonatal administration of FGF2 decreased maternal separation distress calls at P11. • Neonatal FGF2 increased positive affect during exploration and play in juveniles. • Neonatal FGF2 altered expression of the mu opioid receptor and prodynorphin. In previous studies, early-life fibroblast growth factor-2 (FGF2) administration conferred resilience to developing anxiety-like behavior in vulnerable animals in adulthood. To follow up on this work, we administered FGF2 the day after birth to animals that differ in emotional behavior and further explored its long-term effects on affective behavior and circuitry. Selectively-bred "high responder" rats (bHRs) exhibit low levels of anxiety-like and depression-like behavior, whereas selectively-bred "low responders" (bLRs) display high levels of anxiety-like and depression-like behavior. We found that early-life administration of FGF2 decreased negative affect in bLRs during the early post-natal period, as indexed by 40 kHz ultrasonic vocalizations (USVs) in response to a brief maternal separation on PND11. FGF2 also increased positive affect during the juvenile period, as measured by 50 kHz USVs in response to heterospecific hand play ("tickling") after weaning. In general, we found that bHRs produced more 50 kHz USVs than bLRs. In adulthood, we measured opioid ligand and receptor expression in brain regions implicated in USV production and affect regulation by mRNA in situ hybridization. Within multiple affective brain regions, bHRs had greater expression of the mu opioid receptor than bLRs. FGF2 increased mu opioid expression in bLRs. The bLRs had more kappa and less delta receptor expression than bHRs, and FGF2 increased prodynorphin in bLRs. Our results provide support for further investigations into the role of growth factors and endogenous opioids in the treatment of disorders characterized by altered affect, such as anxiety and depression. [ABSTRACT FROM AUTHOR]

Ultrasonic vocalizations (USV) of mice are produced in and emitted by the larynx. However, which anatomical elements of the mouse larynx are involved and to which aspects of USV they contribute is not clear. Frequency and amplitude parameters of mice, deficient in the clock gene Period1 (mPer1 −/− mice) are distinguishably different compared to C3H wildtype (WT) controls. Because structural differences in the larynx may be a reason for the different USV observed, we analyzed laryngeal anatomy of mPer1 −/− mice and WT control animals using micro-computed-tomography and stereology. In mPer1 −/− mice, we found laryngeal cartilages to be normally arranged, and the thyroid, arytenoid and epiglottal cartilages were similar in diameter and volume measurements, compared to WT mice. However, in the cricoid cartilage, a significant difference in the dorso-ventral diameter and volume was evident. Our findings imply that laryngeal morphology is affected by inactivation of the clock gene Period1 in mice, which may contribute to their abnormal USV. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that gestational or developmental vitamin D (DVD) deficiency is associated with an increased risk of autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by impairments in social interaction, lack of verbal and non-verbal communications, stereotyped repetitive behaviors and hyper-activities. There are several other clinical features that are commonly comorbid with ASD, including olfactory impairments, anxiety and delays in motor development. Here we investigate these features in an animal model related to ASD—the DVD-deficient rat. Compared to controls, both DVD-deficient male and female pups show altered ultrasonic vocalizations and stereotyped repetitive behavior. Further, the DVD-deficient animals had delayed motor development and impaired motor control. Adolescent DVD-deficient animals had impaired reciprocal social interaction, while as adults, these animals were hyperactive. The DVD-deficient model is associated with a range of behavioral features of interest to ASD. [ABSTRACT FROM AUTHOR]

Studies determining and categorizing ultrasonic calls in mammals have generally been limited to laboratory experiments with mice and rats or field research on bats. However, recent studies have discovered high-frequency sounds in several mammalian taxa. We describe the vocal repertoire of high-frequency calls in two species of North American flying squirrels (Glaucomys sabrinus and G. volans). We collected passive recordings from captive colonies of G. sabrinus and G. volans to generate a library of calls for each species. Using visual and auditory assessments, as well as quantitative measurements (i.e. spectral and temporal characteristics), we identified 10 specific call-types for G. sabrinus and 27 specific call-types for G. volans. The most common call-types emitted by G. sabrinus included arc chirps, tonal chirps, two-toned chirps, trills, and upsweeps; and for G. volans included arc chirps, barks, descending crows, tonal chirps, and trills. Additionally, we recorded two call-types made by G. volans juveniles: trills and tonal chirps. Most call-types emitted by G. sabrinus were also emitted by G. volans, showing overlap in the repertoire of both species, although variation between species is evident in certain call-types. We also found both species displayed evidence of frequency alteration (i.e. modification of the frequency of one squirrel's call when simultaneously calling with another squirrel using similar call-types). Our call library demonstrates a complex vocal range of tonal and frequency-modulated calls emitted by both species. Acoustic detection of North American flying squirrels is a new monitoring technique that can be used for conservation and management purposes. Differences in the trills, tonal chirps, and arc chirps provide a means to distinguish calls between these species. Increasing understanding of behavior associated with vocalizations may provide a more complete understanding of flying squirrel ecology, including intra- and interspecific interactions. [ABSTRACT FROM AUTHOR]

Rats communicate using ultrasonic vocalizations (USV) throughout their life when confronted with emotionally stimulating situations, either negative or positive. The context of USV emission and the psychoacoustic characteristics of the vocalizations change greatly between infancy and adulthood. Importantly, the production of USV is tightly coordinated with respiration, and respiratory rhythm is known to influence brain activity and cognitive functions. This review goes through the acoustic characteristics and mechanisms of production of USV both in infant and adult rats and emphasizes the tight relationships that exist between USV emission and respiration throughout the rat’s development. It further describes how USV emission and respiration collectively affect brain oscillatory activities. We discuss the possible association of USV emission with emotional memory processes and point out several avenues of research on USV that are currently overlooked and could fill gaps in our knowledge.

Ultrasonic vocalizations (USVs) are well-established markers of motivational and emotional status. Recent work from our lab has provided novel evidence for a role of USVs in models of ethanol (EtOH) use. For instance, USV acoustic characteristics can be used to accurately discriminate between rats selectively bred for high EtOH intake (e.g., alcohol-preferring (P) and high-alcohol-drinking (HAD)) versus EtOH-avoiding (e.g., alcohol-non-preferring (NP) and low-alcohol-drinking (LAD)) strains, as well as differentiate between male and female rats. In the present study we sought to explore the effect of age and alcohol availability on spontaneously emitted 50–55 kHz frequency modulated (FM) and 22–28 kHz USVs in adult, male Long–Evans rats. With the hypothesis that age and alcohol experience influence spontaneous USV emissions, we examined USV data collected across a 24-week intermittent EtOH access experiment in male Long–Evans rats. USV counts and acoustic characteristic (i.e., mean frequency, duration, bandwidth and power) data revealed distinct age-dependent phenotypes in both 50–55 kHz FM and 22–28 kHz USV transmission patterns that were modulated by EtOH exposure. These results highlight the influence of age and EtOH experience on the unique emotional phenotypes of male Long–Evans rats.

Recently, the putative association between selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy and the development of social disorders in children has gained increased attention. However, clinical studies struggle with the confounding effects of maternal depression typically co-occurring with antidepressant treatment. Furthermore, preclinical studies using an animal model of maternal depression to study effects of perinatal SSRI exposure on offspring social behavior are limited. Therefore, the aim of this study was to investigate effects of perinatal fluoxetine exposure on juvenile and adult social behavior in male and female rat offspring, using an animal model of maternal vulnerability. We exposed heterozygous serotonin transporter (SERT) deficient female rats to early life maternal separation stress, and used this as a model for maternal vulnerability. Control and early life stressed heterozygous serotonin transporter knockout (SERT) dams were treated with the SSRI fluoxetine or vehicle throughout gestation and lactation. Subsequently, both male and female wildtype (SERT+/+) and heterozygous (SERT+/-) rat offspring were tested for pup ultrasonic vocalizations (USVs), juvenile social play behavior and adult social interaction. Fluoxetine treatment of the dams resulted in a reduced total USV duration in pups at postnatal day 6, especially in SERT+/+ males. Perinatal fluoxetine exposure lowered social play behavior in male offspring from both control and early life stressed dams. However, in females a fluoxetine-induced reduction in juvenile play behavior was only present in offspring from control dams. Offspring genotype did not affect juvenile play behavior. Despite fluoxetine-induced behavioral effects at juvenile age, fluoxetine reduced male adult social behavior in offspring from control dams only. Effects of fluoxetine on female adult social behavior were virtually absent. Interestingly, early life stress in dams increased adult social exploration in vehicle exposed SERT+/+ female offspring and total social behavior in fluoxetine exposed adult SERT+/- male offspring. Furthermore, SERT+/- males appeared less social during adulthood compared to SERT+/+ males. Overall, the present study shows that chronic blockade of the serotonin transporter by fluoxetine during early development has a considerable impact on pup USVs, juvenile social play behavior in both male and female offspring, and to a lesser extent on male social interaction in adulthood.

The cross-disorder risk gene CACNA1C is strongly implicated in multiple neuropsychiatric disorders, including autism spectrum disorder (ASD), bipolar disorder (BPD) and schizophrenia (SCZ), with deficits in social functioning being common for all major neuropsychiatric disorders. In the present study, we explored the role of Cacna1c in regulating disorder-relevant behavioral phenotypes, focusing on socio-affective communication after weaning during the critical developmental period of adolescence in rats. To this aim, we used a newly developed genetic Cacna1c rat model and applied a truly reciprocal approach for studying communication through ultrasonic vocalizations, including both sender and receiver. Our results show that a deletion of Cacna1c leads to deficits in social behavior and pro-social 50-kHz ultrasonic communication in rats. Reduced levels of 50-kHz ultrasonic vocalizations emitted during rough-and-tumble play may suggest that Cacna1c haploinsufficient rats derive less reward from playful social interactions. Besides the emission of fewer 50-kHz ultrasonic vocalizations in the sender, Cacna1c deletion reduced social approach behavior elicited by playback of 50-kHz ultrasonic vocalizations. This indicates that Cacna1c haploinsufficiency has detrimental effects on 50-kHz ultrasonic communication in both sender and receiver. Together, these data suggest that Cacna1c plays a prominent role in regulating socio-affective communication in rats with relevance for ASD, BPD and SCZ. This article has an associated First Person interview with the first author of the paper.

Highlights • Differential cFos activation to 22 kHz and 55 kHz ultrasonic vocalization playback. • Playback of aversive vocalizations increases anxiety-like behaviors. • 22 kHz playback increases basolateral amygdala and BNST cFos activation. • No changes in heart rate indices during vocalization playback. • First report of increased anxiety during 22 kHz USV in elevated zero maze. Abstract The communicative role of ultrasonic vocalizations (USVs) in rats is well established, with distinct USVs indicative of different affective states. USVs in the 22 kHz range are typically emitted by adult rats when in anxiety- or fear-provoking situations (e.g. predator odor, social defeat), while 55 kHz range USVs are typically emitted in appetitive situations (e.g., play, anticipation of reward). Previous work indicates that USVs (real-time and playback) can effectively communicate these affective states and influence changes in behavior and neural activity of the receiver. Changes in cFos activation following 22 kHz USVs have been seen in cortical and limbic regions involved in anxiety, including the basolateral amygdala (BLA). However, it is unclear how USV playback influences cFos activity within the bed nucleus of the stria terminalis (BNST), a region also thought to be critical in processing anxiety-related information, and the nucleus accumbens, a region associated with reward. The present work sought to characterize distinct behavioral, physiological, and neural responses in rats presented with aversive (22 kHz) compared to appetitive (55 kHz) USVs or silence. Our findings show that rats exposed to 22 kHz USVs: 1) engage in anxiety-like behaviors in the elevated zero maze, and 2) show distinct patterns of cFos activation within the BLA and BNST that contrast those seen in 55 kHz playback and silence. Specifically, 22 kHz USVs increased cFos density in the anterodorsal nuclei, while 55 kHz playback increased cFos in the oval nucleus of the BNST, without significant changes within the nucleus accumbens. These results provide important groundwork for leveraging ethologically-relevant stimuli in the rat to improve our understanding of anxiety-related responses in both typical and pathological populations. [ABSTRACT FROM AUTHOR]

Recently, the putative association between selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy and the development of social disorders in children has gained increased attention. However, clinical studies struggle with the confounding effects of maternal depression typically co-occurring with antidepressant treatment. Furthermore, preclinical studies using an animal model of maternal depression to study effects of perinatal SSRI exposure on offspring social behavior are limited. Therefore, the aim of this study was to investigate effects of perinatal fluoxetine exposure on juvenile and adult social behavior in male and female rat offspring, using an animal model of maternal vulnerability. We exposed heterozygous serotonin transporter (SERT) deficient female rats to early life maternal separation stress, and used this as a model for maternal vulnerability. Control and early life stressed heterozygous serotonin transporter knockout (SERT) dams were treated with the SSRI fluoxetine or vehicle throughout gestation and lactation. Subsequently, both male and female wildtype (SERT+/+) and heterozygous (SERT+/-) rat offspring were tested for pup ultrasonic vocalizations (USVs), juvenile social play behavior and adult social interaction. Fluoxetine treatment of the dams resulted in a reduced total USV duration in pups at postnatal day 6, especially in SERT+/+ males. Perinatal fluoxetine exposure lowered social play behavior in male offspring from both control and early life stressed dams. However, in females a fluoxetine-induced reduction in juvenile play behavior was only present in offspring from control dams. Offspring genotype did not affect juvenile play behavior. Despite fluoxetine-induced behavioral effects at juvenile age, fluoxetine reduced male adult social behavior in offspring from control dams only. Effects of fluoxetine on female adult social behavior were virtually absent. Interestingly, early life stress in dams increased adult social exploration in vehicle exposed SERT+/+ female offspring and total social behavior in fluoxetine exposed adult SERT+/- male offspring. Furthermore, SERT+/- males appeared less social during adulthood compared to SERT+/+ males. Overall, the present study shows that chronic blockade of the serotonin transporter by fluoxetine during early development has a considerable impact on pup USVs, juvenile social play behavior in both male and female offspring, and to a lesser extent on male social interaction in adulthood. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) increases metabolic neuronal activity in the mesolimbic dopamine (DA) system and mediates the reinforcing effect. To explore the underlying mechanism of acupuncture intervention in reducing METH-induced behaviors, we investigated the effect of acupuncture on locomotor activity, ultrasonic vocalizations, extracellular DA release in the nucleus accumbens (NAcs) using fast-scan cyclic voltammetry and alterations of brain temperature (an indicator of local brain metabolic activity) produced by METH administration. When acupuncture was applied to HT7, but not TE4, both locomotor activity and 50-kHz ultrasonic vocalizations were suppressed in METH-treated rats. Acupuncture at HT7 attenuated the enhancement of electrically stimulated DA release in the NAc of METH-treated rats. Systemic injection of METH produced a sustained increase in NAc temperature, which was reversed by the DA D1 receptor antagonist SCH 23390 or acupuncture at HT7. Acupuncture inhibition of METH-induced NAc temperature was prevented by pre-treatment with a group II metabotropic glutamate receptors (mGluR2/3) antagonist EGLU into the NAc or mimicked by injection of an mGluR2/3 agonist DCG-IV into the NAc. These results suggest that acupuncture reduces extracellular DA release and metabolic neuronal activity in the NAc through activation of mGluR2/3 and suppresses METH-induced affective states and locomotor behavior. [ABSTRACT FROM AUTHOR]

Abstract Methoxetamine (MXE) is a novel psychoactive substance that can induce several short-term effects on emotional states and behavior. However, little is known about the persistent emotional and behavioral effects of MXE. Moreover, neurotoxic effects of MXE have been hypothesized, but never demonstrated in vivo. To clarify these issues, rats received repeated treatment with MXE every other day (0.1–0.5 mg/kg, i.p., × 5), and 7 days later they were challenged with MXE (0.1–0.5 mg/kg, i.p.). Behavioral effects of MXE were first evaluated by measuring emission of ultrasonic vocalizations and locomotor activity after each administration. Thereafter, persistent behavioral effects of MXE were evaluated, starting 8 days after challenge, through elevated plus maze, spontaneous alternation, novel object recognition, and marble burying tests. After completion of behavioral analysis, neurotoxic effects of MXE were evaluated by measuring densities of dopamine transporter, tyrosine hydroxylase, and serotonin transporter in various brain regions. Repeated treatment and challenge with MXE affected neither calling behavior nor locomotor activity of rats. Conversely, rats previously treated with MXE exhibited behavioral alterations in the elevated plus maze, marble burying and novel object recognition tests, suggestive of increased anxiety and impaired non-spatial memory. Noteworthy, the same rats displayed dopaminergic damage in the medial prefrontal cortex, nucleus accumbens, caudate-putamen, substantia nigra pars compacta , and ventral tegmental area, along with accumbal serotonergic damage. Our findings show for the first time that repeated administration of MXE induces persistent behavioral abnormalities and neurotoxicity in rats, which can help elucidating the risks associated with human MXE consumption. Graphical abstract Image 1 Highlights • Methoxetamine is a novel psychoactive substance used as recreational drug. • Little is known about the enduring effects of methoxetamine. • We evaluated behavior and neurotoxicity in rats repeatedly exposed to methoxetamine. • Methoxetamine induced persitent changes in emotional state and non-spatial memory. • Methoxetamine persistently damaged the mesocorticolimbic dopaminergic system. [ABSTRACT FROM AUTHOR]

Abstract Systemic pharmacological manipulation of dopamine (DA) signaling has been central to many investigations of 50 kHz ultrasonic vocalizations (USVs) in the rat. In particular, the indirect DA releaser d -amphetamine (AMPH) has been used extensively in many such investigations. The possible unique character of the native transmitter relative to DA-stimulating drugs such as AMPH in inducing and modulating emission of 50 kHz USVs has not been investigated. Adult male Long Evans rats were tested with intracerebral application of DA into the nucleus accumbens shell at several doses (3.75 μg–120 μg) to determine its capacity to induce 50 kHz USV emission. Additionally, the call profile characteristics of intracerebral DA injections were compared with those of intracerebral application of AMPH. Results indicated that local increases in DA signaling within the nucleus accumbens shell are sufficient to increase 50 kHz call rate, reduce latency to call, and increase the degree of frequency modulation of emitted USVs. However, our results found that microinjections of DA were not as efficacious in either inducing 50 kHz USVs or increasing frequency modulation without antagonism of the dopamine reuptake transporter when compared with AMPH. In summary, these results support the notion that the native transmitter DA is driving the increase in frequency modulation seen after administration of DA stimulating drugs. These results also suggest that drugs affecting dopamine may be altering the 50 kHz call profile in a distinct manner from the native transmitter and thus caution should be used in interpreting their effects. Highlights • Direct injection of dopamine into the nucleus accumbens induces 50 kHz USVs. • Dopamine capable of reducing latency to call and increasing frequency modulation. • Compared with AMPH dopamine is less effective at inducing 50 kHz USVs. • Differences between dopamine and AMPH in altering 50 kHz call profile indicated. [ABSTRACT FROM AUTHOR]

Objective: Age-related muscle atrophy of the laryngeal muscles contributes to presbyphonia. Remodeling of the neuromuscular junction is one aspect underlying age-related muscle atrophy. Although muscle disuse has been shown to exacerbate age-related neuromuscular changes in the limb muscles, it is unknown if reduced vocal use has a similar effect in the laryngeal muscles. The objective of this study was to examine the use of social isolation as a novel method to reduce vocal use in old rats-and the impact of that reduced vocal use on ultrasonic vocalization acoustics and neuromuscular junction morphology in the thyroarytenoid muscle.Study Design: Animal group comparison.Methods: Old F344/BN rats (31 months of age) were socially isolated (n = 8) or communally housed (n = 8) for 8 weeks. Effect of housing condition on ultrasonic vocalization acoustics was assessed by calculating the changes in vocalization fundamental frequency and amplitude from baseline to 8 weeks. Neuromuscular junction morphology was measured in the lateral and medial portions of the thyroarytenoid muscle at the conclusion of the experiment.Results: Vocalization amplitude decreased by a mean of -4.4 dB (standard deviation [SD], 4.49) after social isolation, whereas amplitude increased by a mean of 5.7 dB (SD, 5.07) in the communally housed rats (P = 0.002). There was no significant difference in the change in fundamental frequency between groups. Furthermore, there were no group differences in any measure of neuromuscular junction morphology.Conclusion: These results suggest that neuromuscular junctions in the thyroarytenoid muscle of old rats are unaffected by 8 weeks of social isolation, despite functional changes in vocalizations.Level Of Evidence: NA Laryngoscope, 129:E9-E14, 2019. [ABSTRACT FROM AUTHOR]

Purpose of the Review: Rodents produce ultrasonic vocalizations (USV) under different social contexts, including courtship and reproduction. The present review aims to summarize the behavioral, bioacoustical, and physiological evidence that USV are reliable signals of sexual motivation in both male and female rodents.Recent Findings: USV are actively produced by both sexes during sexual interactions, contrary to earlier assumptions. Male-typical and female-typical vocal behaviors can be identified. Calling rates and acoustic parameters, such as call duration, frequency, and energy, can be modulated rapidly over time by motivational state and sexual context. USV produced in response to sexual context could be regulated by the brain on a moment-to-moment basis through non-classical mechanisms of steroid action. Finally, I provide some practical considerations for the acoustic and statistical analyses of these vocal signals.Summary: USV can be used as signals of sexual motivation in both sexes to study brain and hormonal mechanisms underlying sexual behavior or sexual differentiation. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Avisoft detected more vocalizations overall than Ultravox. • Avisoft detected more total vocalizations at 50, 60, and 70 kHz than Ultravox. • There is only a medium correlation between systems despite congruent parameters. Abstract Alterations in early-life communicative behaviors are a common feature of neurodevelopmental conditions, such as autism and epilepsy. One method of investigating communication in murine models is through analyzing ultrasonic vocalizations. These vocalizations are commonly recorded with either the Avisoft or the Ultravox recording programs. However, since no study has compared whether the systems are equally sensitive, the findings in one program may not be reproducible in the other. To directly compare the two programs, we elicited vocalizations from male and female 129SvEvTac and C57BL/6 mouse pups via the maternal isolation paradigm, recording vocalizations simultaneously with both systems. We held the detection parameters identical for each system and found that there was only a medium correlation between Avisoft and Ultravox overall. Further analysis indicated that Avisoft detected more total vocalizations, as well as more vocalizations at the set frequencies of 50, 60, and 70 kHz than Ultravox, p <.05. No statistically significant difference was present at 80 kHz. These findings demonstrate that different recording systems do not detect the same quantity of vocalizations as one another, even when detection parameters are congruent. Therefore, it may be useful to revisit previous negative results obtained with Ultravox and repeat the experiments using Avisoft. Ultimately, ultrasonic vocalizations are a valuable tool, capable of examining early-life phenotypes. However, a more thorough understanding of the relationships between recording systems is necessary to achieve a more comprehensive and reproducible assessment of vocalizing behaviors. [ABSTRACT FROM AUTHOR]

Acoustic signals are widely used as courtship signals in the animal kingdom. It has long been known that male mice emit ultrasonic vocalizations (USVs) in the presence of female mice or in response to female secretions. This observation led to the hypothesis that male USVs play a role in courtship behavior. Although previous studies showed that female mice have a social partner preference for vocalizing males, it is not known if they exhibit a sexual partner preference when given a choice. To address this issue, we examined the copulatory behaviors of female mice with either devocalized males (with or without the playback of the USVs) or sham‐operated males in 2 different behavioral paradigms: the no‐choice paradigm in the home cage of a male mouse (without choice of mating partners) or the mate‐choice paradigm in a 3‐chambered apparatus (with choice of mating partners). In the no‐choice paradigm, female mice exhibited comparable sexual receptivity with sham‐operated and devocalized males. In addition, we found that female mice showed more approach behavior towards devocalized males when male USVs were played back. In the mate‐choice paradigm, female mice visited more frequently and stayed longer with sham‐operated than devocalized males. Furthermore, we showed that female mice received more intromissions from sham‐operated males than devocalized males. In summary, our results suggested that, although female mice can copulate equally with both devocalized and vocalizing males when given no choice of mating partner, female mice exhibit both sexual and social partner preferences for vocalizing males in the mate‐choice paradigm. [ABSTRACT FROM AUTHOR]

Abstract The emission of 50 kHz ultrasonic vocalizations (USVs) by rats is thought to represent a measurable expression of the individuals underlying emotional state. These calls are also posited as fulfilling important communicative functions among conspecifics. In addition to social situations, 50 kHz USVs are recorded in a variety of reward-related contexts including sugary foods and drink, consumable ethanol, and drugs of abuse. The current study sought to directly compare several of these behavioural contexts in their capability to induce and modulate 50 kHz USV emission in adult male rats. Using two social conditions (exposure of naïve rat to a naturally cycling female and reuniting with a same-sex cage partner) and two non-social conditions (access to consumables as Fruit Loops or 2% ethanol v/v), we analyzed USVs recorded in 6 stimulus-presentation sessions. Only the female-exposure condition was found to increase 50 kHz call rate significantly over baseline, and this induction sensitized across 4 standard recording sessions. The use of a same-sex cage-mate and the two consumable food rewards did not elicit higher than baseline 50 kHz calling. None of the behavioural contexts altered the acoustic parameters (peak frequency, duration, and bandwidth) of emitted 50 kHz calls. In counter-balanced recording sessions, calling across all groups was significantly reduced by pre-treatment with the dopamine antagonist haloperidol compared with vehicle. Non-social conditions appeared to induce a greater proportion of flat calls at the expense of non-trill FM calls, while the reverse was seen for social conditions. However, the type of food reward and the type of social context mattered for proportion of flat and trill calls respectively. When compared with a control, access to sugary food but not ethanol induced a greater proportion of flat calls, and the female but not the cage-mate stimulus induced a greater proportion of trill calls. Highlights • 50 kHz USVs recorded in multiple sessions in response to distinct behavioural contexts. • Analysis reveals no differences in acoustic features of calls in these contexts. • 50 kHz USVs to both social and non-social contexts depended on dopamine signaling. • Consumable food-rewards appear to preferentially increase proportion of flat calls. • Social contexts appear to preferentially increase FM calls, with female inducing trills. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders, characterized by early-onset deficits in social behavior and communication across multiple contexts, together with restricted, repetitive patterns of behavior, interests, or activities. ASD is among the most heritable neuropsychiatric conditions with heritability estimates higher than 80%, and while available evidence points to a complex set of genetic factors, the SHANK (also known as ProSAP) gene family has emerged as one of the most promising candidates. Several genetic Shank mouse models for ASD were generated, including Shank1 knockout mice. Behavioral studies focusing on the Shank1 knockout mouse model for ASD included assays for detecting ASD-relevant behavioral phenotypes in the following domains: (I) social behavior, (II) communication, and (III) repetitive and stereotyped patterns of behavior. In addition, assays for detecting behavioral phenotypes with relevance to comorbidities in ASD were performed, including but not limited to (IV) cognitive functioning. Here, we summarize and discuss behavioral and neuronal findings obtained in the Shank1 knockout mouse model for ASD. We identify open research questions by comparing such findings with the symptoms present in humans diagnosed with ASD and carrying SHANK1 deletions. We conclude by discussing the implications of the behavioral and neuronal phenotypes displayed by the Shank1 knockout mouse model for the development of future pharmacological interventions in ASD. [ABSTRACT FROM AUTHOR]

Humans exhibit broad heterogeneity in affiliative social behavior. Twin and family studies show that individual differences in core dimensions of social behavior are heritable, yet there are knowledge gaps in understanding the underlying genetic and neurobiological mechanisms. Animal genetic reference panels (GRPs) provide a tractable strategy for examining the behavioral and genetic architecture of complex traits. Here, using males from 50 mouse strains from the BXD GRP, 4 domains of affiliative social behavior--social approach, social recognition, direct social interaction (DSI) (partner sniffing) and vocal communication--were examined in 2 widely used behavioral tasks--the 3-chamber and DSI tasks. There was continuous and broad variation in social and nonsocial traits, with moderate to high heritability of social approach sniff preference (0.31), ultrasonic vocalization (USV) count (0.39), partner sniffing (0.51), locomotor activity (0.54-0.66) and anxiety-like behavior (0.36). Principal component analysis shows that variation in social and nonsocial traits are attributable to 5 independent factors. Genome-wide mapping identified significant quantitative trait loci for USV count on chromosome (Chr) 18 and locomotor activity on Chr X, with suggestive loci and candidate quantitative trait genes identified for all traits with one notable exception--partner sniffing in the DSI task. The results show heritable variation in sociability, which is independent of variation in activity and anxiety-like traits. In addition, a highly heritable and ethological domain of affiliative sociability--partner sniffing-- appears highly polygenic. These findings establish a basis for identifying functional natural variants, leading to a new understanding typical and atypical sociability. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) encompasses several neurodevelopmental conditions characterized by communication and social impairment, as well as repetitive patterns of behavior. However, it can co-occur with other mental conditions such as anxiety. The massive use of chlorpyrifos (CPF) has been linked to the increased prevalence of developmental disorders. Likewise, ASD has also been closely linked to a wide variety of genetic factors. The aims of the present investigation are to study how gestational CPF exposure and APOE polymorphism affects communication skills, early development and mid-term anxiety-like behaviors, as well as, changes in gene expression related to the cholinergic system. C57BL/6J and humanized apoE3 and apoE4 homozygous mice were exposed to 0 or 1 mg/kg/day of CPF through the diet, from gestational day (GD) 12–18. In addition, a group of C57BL/6J females were injected subcutaneously with 300 mg/kg/day of valproic acid (VPA) on GD 12 and 13. This group was used as a positive control for studying some core and associated autism-like behaviors. Communication skills by means of ultrasonic vocalizations and physical/motor development were assessed during the preweaning period, whereas locomotor activity, anxiety-like behaviors and the gene expression of cholinergic elements were evaluated during adolescence. Our results showed that C57BL/6J mice prenatally exposed to CPF or VPA showed a decrease in body weight and a delay in eye opening. Communication and anxiety behavior were affected differently depending on treatment, while gene expression was altered by sex and treatment. In addition, none of the parameters evaluated in apoE transgenic mice exposed to CPF were affected, but there were differences between genotypes. Therefore, we suggest that prenatal CPF exposure and VPA produce divergent effects on communication and anxiety. • Prenatal exposure to CPF and VPA produced opposite effects on communication skills. • VPA-treated mice showed autism-like behaviors in all parameters evaluated. • VPA-treated females showed a decrease in VChAT expression in hippocampus. • Behavioral differences between the APOE genotype were observed at adolescence. [ABSTRACT FROM AUTHOR]

Grooming is a common readout in multiple rat models of neuropsychiatric diseases. It is usually associated with distress and negative emotionality, but also with emotional de-arousal after stress. These seemingly conflicting interpretations may result from specific grooming sequences appearing at different arousal levels and during distinct phases of the stress response. To further explore this hypothesis, we analyzed how distinct stressors affect grooming syntaxis and kinetics. To that end, we explored the independent and interacting effects of foot shocks, corticosterone (CORT), and novelty on exploratory activity, grooming, and ultrasonic vocalizations (USVs) in an open-field test (OF). Wistar rats were intraperitoneally injected either with vehicle or CORT, placed in a chamber where half of them were foot-shocked and then assessed in the OF. The next day, animals were re-exposed to the shock chamber and then tested in the OF without receiving any treatment. On day 1, foot shocks and –to a less extent CORT– increased freezing and inhibited rearing in the chamber, but only foot shocks increased distress USVs. In the OF, both treatments suppressed complex grooming, with foot-shocks also inhibiting exploration and CORT marginally reducing rearing. On day 2, foot-shocked rats showed conditioned fear when re-exposed to the chamber. When tested in the OF, foot-shocked and CORT-treated animals still showed low levels of complex grooming, with the former group also showing increased distress USVs. In this study, all different stressors inhibited complex grooming, suggesting an inverse association between these grooming subtypes and negative emotionality. • Foot shocks (FS) and CORT reduced exploratory behaviors in the Open Field (OF). • Both stressors reduced complex grooming but only FS induced 22-kHz calls in the OF. • Foot-shocked rats showed conditioned fear when re-exposed to the FS chamber 24 h later. • Conditioned fear reduced complex grooming and evoked 22-kHz calls in the OF. • All stressors inhibited complex grooming while novelty habituation promoted it. [ABSTRACT FROM AUTHOR]

Mice produce various sounds within the ultrasonic range in social contexts. Although these sounds are often used as an index of sociability in biomedical research, their biological significance remains poorly understood. We previously showed that mice repeatedly produced calls in a sequence (i.e. calling bout), which can vary in their structure, such as Simple, Complex or Harmonics. In this study, we investigated the use of the three types of calling bouts in different sociosexual interactions, including both same- and opposite-sex contexts. In same-sex contexts, males typically produced a Simple calling bout, whereas females mostly produced a Complex one. By contrast, in the opposite-sex context, they produced all the three types of calling bouts, but the use of each calling type varied according to the progress and mode of sociosexual interaction (e.g. Harmonic calling bout was specifically produced during reproductive behaviour). These results indicate that mice change the structure of calling bout according to sociosexual contexts, suggesting the presence of multiple functional signals in their ultrasonic communication.

Mice produce ultrasonic vocalizations (USVs) in a variety of social situations, and USVs have been leveraged to study many neurological diseases including verbal dyspraxia, depression, autism and stuttering. Pups produce isolation calls, a common USV, spontaneously when they are isolated from their mother during the first 2 weeks of life. Several genetic manipulations affect (and often reduce) pup isolation calls in mice. To facilitate the use of this assay as a means of testing whether significant functional differences in genotypes exist instead of contextual differences, we test the variability inherent in many commons measures of mouse vocalizations. Here we use biological consistency as a way of determining which are reproducible in mouse pup vocalizations. We present a comprehensive analysis of the normal variability of these vocalizations in groups of mice, individual mice and different strains of mice. To control for maturation effects, we recorded pup isolation calls in the same group of C57BL/6J 5 days old mice twice, with 1 h of rest in between recordings. In almost all cases, the group averages between the first and second recordings were the same. We also found that there were high correlations in some parameters in individual mice across recording while others were not well correlated. These findings could be replicated for the majority of features in a separate group of C57BL/6J mice and a group of 129/SvEvBrd-C57BL/6J mice. The averages of these mouse USV features are highly consistent and represent a robust assay to test the effects of genetic and other interventions in the experimental setting.