Sex-dependent effects of Cacna1c haploinsufficiency on behavioral inhibition evoked by conspecific alarm signals in rats

Wöhr, Markus; Willadsen, Maria; Kisko, Theresa M.; Schwarting, Rainer K.W.; Fendt, Markus

doi:10.1016/j.pnpbp.2019.109849

Cited by 21 publications

(35 citation statements)

References 59 publications

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“…Playback of alarm USVs to adult rats also affects behavior differently between sexes. A playback of 22 kHz alarm USVs resulted in more long-lasting behavioral inhibition in female rats than male rats [78]. This finding highlights that although rats may have hormone-mediated, sexually dimorphic USV rates and different acoustic characteristics, these differences may not be directly related to laryngeal differences but rather differences in behavior mediated by the central nervous system.…”

Section: Alarm 22 Khz Usvsmentioning

confidence: 81%

“…This suggested that female USVs may be indicative of sexual motivation. Other studies found that during rough-and-tumble play, levels of 50 kHz vocalizations was decreased as a result of Cacna1c haploinsufficiency, a gene implicated in social signal processing, which was more robustly noted in males than females [78]. Additionally, studies have explored acoustical parameter differences in male and female rats in isolation.…”

Section: Adult 50 Khz Usv Acousticsmentioning

confidence: 99%

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Biological and Acoustic Sex Differences in Rat Ultrasonic Vocalization

et al. 2021

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The rat model is a useful tool for understanding peripheral and central mechanisms of laryngeal biology. Rats produce ultrasonic vocalizations (USVs) that have communicative intent and are altered by experimental conditions such as social environment, stress, diet, drugs, age, and neurological diseases, validating the rat model’s utility for studying communication and related deficits. Sex differences are apparent in both the rat larynx and USV acoustics and are differentially affected by experimental conditions. Therefore, the purpose of this review paper is to highlight the known sex differences in rat USV production, acoustics, and laryngeal biology detailed in the literature across the lifespan.

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Section: Alarm 22 Khz Usvsmentioning

confidence: 81%

Section: Adult 50 Khz Usv Acousticsmentioning

confidence: 99%

Biological and Acoustic Sex Differences in Rat Ultrasonic Vocalization

et al. 2021

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“…Other than solely expressing anxiety and fear, 22-kHz USV are thought to function as alarm calls to warn conspecifics about threats and were shown to evoke a fear response in receiver rats [42,65]. The latter was also observed during social fear conditioning [59,67,68] and confirmed in playback studies, where 22-kHz USV induced behavioral inhibition in receiver rats [43,69]. Supporting a communicative function, 22-kHz USV emission was reported to be potentiated by the presence of conspecifics [42] and it appears possible that this audience effect is more prominent in female than male rats.…”

Section: Sex Differences In Fear-related Behaviormentioning

confidence: 83%

Fear Extinction and Predictive Trait-Like Inter-Individual Differences in Rats Lacking the Serotonin Transporter

Willadsen

Uengoer

Sługocka

et al. 2021

IJMS

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Anxiety disorders are associated with a failure to sufficiently extinguish fear memories. The serotonergic system (5-hydroxytryptamine, 5-HT) with the 5-HT transporter (5-HTT, SERT) is strongly implicated in the regulation of anxiety and fear. In the present study, we examined the effects of SERT deficiency on fear extinction in a differential fear conditioning paradigm in male and female rats. Fear-related behavior displayed during acquisition, extinction, and recovery, was measured through quantification of immobility and alarm 22-kHz ultrasonic vocalizations (USV). Trait-like inter-individual differences in novelty-seeking, anxiety-related behavior, habituation learning, cognitive performance, and pain sensitivity were examined for their predictive value in forecasting fear extinction. Our results show that SERT deficiency strongly affected the emission of 22-kHz USV during differential fear conditioning. During acquisition, extinction, and recovery, SERT deficiency consistently led to a reduction in 22-kHz USV emission. While SERT deficiency did not affect immobility during acquisition, genotype differences started to emerge during extinction, and during recovery rats lacking SERT showed higher levels of immobility than wildtype littermate controls. Recovery was reflected in increased levels of immobility but not 22-kHz USV emission. Prominent sex differences were evident. Among several measures for trait-like inter-individual differences, anxiety-related behavior had the best predictive quality.

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“…Importantly, we found that approach occurs specifically in response to signals with frequencies typical for 50-kHz USV, because no such responses were observed when rats were exposed to background noise or 22-kHz USV (e.g. Wö hr and Fendt et al, 2018;Wö hr et al, 2020). Also, 50-kHz USV effectiveness is dependent on the animals' developmental stage, because approach proved Importantly, most of the abovementioned evidence is based on results obtained during a first exposure to 50-kHz USV playback, since the prominent social approach response induced during the first exposure substantially declines with repeated 50-kHz USV playback even when performed several days later (Wö hr and Schwarting, 2012;Schö nfeldet al, 2020).…”

Section: Introductionmentioning

confidence: 89%

Limited generalizability, pharmacological modulation, and state-dependency of habituation towards pro-social 50-kHz calls in rats

et al. 2021

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Communication constitutes a fundamental component of mammalian social behavior. Rats are highly social animals and emit 50-kHz ultrasonic vocalizations (USV), which function as social contact calls. Playback of 50-kHz USV leads to strong and immediate social approach responses in receiver rats, but this response is weak or even absent during repeated 50-kHz USV playback. Given the important role of 50-kHz USV in initiating social contact and coordinating social interactions, the occurrence of habituation is highly unexpected. It is not clear why a social signal characterized by significant incentive salience loses its power to change the behavior of the receiver so rapidly. Here, we show that the habituation phenomenon displayed by rats in response to repeated playback of 50-kHz USV (1) is characterized by limited generalizability because it is present in Wistar but not Sprague-Dawley rats, (2) can be overcome by amphetamine treatment, and (3) depends on the subject's internal state.

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Sex-dependent effects of Cacna1c haploinsufficiency on behavioral inhibition evoked by conspecific alarm signals in rats

Cited by 21 publications

References 59 publications

Biological and Acoustic Sex Differences in Rat Ultrasonic Vocalization

Biological and Acoustic Sex Differences in Rat Ultrasonic Vocalization

Fear Extinction and Predictive Trait-Like Inter-Individual Differences in Rats Lacking the Serotonin Transporter

Limited generalizability, pharmacological modulation, and state-dependency of habituation towards pro-social 50-kHz calls in rats

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