Reduced isolation-induced pup ultrasonic communication in mouse pups lacking brain serotonin

Abstract

BackgroundSerotonin (5-hydroxytryptamine, 5-HT) is a key modulatory neurotransmitter in the mammalian central nervous system (CNS) that plays an important role as a developmental signal. Several lines of evidence associate altered 5-HT signaling with psychopathology in humans, particularly neurodevelopmental disorders such as autism spectrum disorders (ASD). ASD are characterized by persistent social and communication deficits along with stereotyped and repetitive patterns of behavior, with all symptoms emerging early during development.MethodsHere, we employed a mouse model devoid of brain 5-HT due to the lack of the gene encoding tryptophan hydroxylase 2 (Tph2), the initial and rate-limiting enzyme of 5-HT synthesis in the CNS. Tph2 null mutant (Tph2-/-) mice show normal prenatal development; however, they display for yet unknown reasons severe growth retardation during the first postnatal weeks. We investigated, therefore, whether Tph2-/- mice display deficits in isolation-induced ultrasonic vocalizations (USV) as pups during early life. Isolation-induced USV are the most commonly studied behavioral measure to assess developmental delays and communication deficits in rodent models for ASD, particularly as they serve an important communicative function in coordinating mother-pup interactions.ResultsTph2-/- mouse pups displayed a clear deficit in the emission of isolation-induced USV, as compared to heterozygous and wildtype littermates, exactly during growth retardation onset, including reduced call numbers and deficits in call clustering and temporal organization.ConclusionsThe ultrasonic communication impairment displayed by Tph2-/- mouse pups is likely to result in a deficient mother-infant interaction, presumably contributing to their growth retardation phenotype, and represents a prominent feature relevant to ASD.

A giant ankyrin-B mechanism for neuro-diversity/divergence through stochastic ectopic axon projections

“…6a). Similar phenotypes of altered pup USVs are reported in D2 dopamine receptor null mice 36 , tryptophan hydroxylase 2 null mice 37 , and shank3 null mice 38 . Both decreased pup USVs and territory marking are noted in shank1 null mice 39 .…”

Isolation‐induced ultrasonic vocalizations in pups: A comparison between Long‐Evans, Sprague–Dawley, and Wistar rats

“…Whether the different call types in rat pups, such as the present ones, may be differentially effective in this respect, is not known. However, it has been shown that certain spectral features of pup calls, like call length, peak frequency, or amplitude may play a role in mice (Smith, , Ehret, , Liu & Miller, , Wöhr et al, , for review, see Wöhr & D'Amato, ) and that the clustering of call types is affected in mouse pups lacking genes implicated in social behavior and communication (Mosienko et al, ; Sungur et al, ; Wöhr, ). In rats, it was shown that playback of natural isolation‐induced USV leads to maternal search behavior, while no such response was seen in mothers exposed to 40‐kHz sine wave tones (Wöhr & Schwarting, ).…”

“…Furthermore, we aimed to classify these calls into different types, based on observational methods and by means of spectrographic features, since previous studies have shown that pup USV may be assigned to different types, which, dependent on the method, may range between 2 and 13 types (e.g., Brudzynski et al, , Hashimoto, Moritani, Aoki‐Komori, Tanaka, & Saito, ; Zeskind et al, ). While such previous classifications are based on visual inspection of spectrograms, primarily focusing on call shapes, we aimed for a different, and probably less subjective, classification by means of a quantitative approach including acoustic features, such as frequency modulation, peak frequency, and call duration, previously applied in mouse pups (Mosienko, Beis, Alenina, & Wöhr, ; Sungur, Schwarting, & Wöhr, ; Wöhr, ; Wöhr et al, ). Defining call types is important, since certain ones may specifically be affected, for example, by pre‐ or neonatal manipulations (Barren & Gilbertson ; Harmon et al, ; Krüger & Hanganu‐Opatz, ; Tonkiss et al, ), and it is reasonable to assume that different genetic backgrounds, like in the three outbred stocks, may also affect them.…”

The serotonin system in autism spectrum disorder: From biomarker to animal models

“…For example, mice lacking tryptophan hydroxylase 2, responsible for central 5-HT synthesis, show decreased ultrasonic vocalizations, decreased sniffing of social odors, apparent deficits in social memory, and cognitive inflexibility (Kane et al, 2012, Del’Guidice et al, 2014, Mosienko et al, 2015). Mice lacking MAOA, responsible for breaking down 5-HT, show decreased social approach, decreased ultrasonic vocalizations, and impaired reversal learning (Bortolato et al, 2013).…”