Communication Impairment in Ultrasonic Vocal Repertoire during the Suckling Period of Cd157 Knockout Mice: Transient Improvement by Oxytocin.

Olga L Lopatina,Katsuhiko Ishihara,Haruhiro Higashida,Kazumi Furuhara,Alla B Salmina

doi:10.3389/fnins.2017.00266

Abstract

Communication consists of social interaction, recognition, and information transmission. Communication ability is the most affected component in children with autism spectrum disorder (ASD). Recently, we reported that the CD157/BST1 gene is associated with ASD, and that CD157 knockout (Cd157−/−) mice display severe impairments in social behavior that are improved by oxytocin (OXT) treatment. Here, we sought to determine whether Cd157−/− mice can be used as a suitable model for communication deficits by measuring ultrasonic vocalizations (USVs), especially in the early developmental stage. Call number produced in pups due to isolation from dams was higher at postnatal day (PND) 3 in knockout pups than wild-type mice, but was lower at PNDs 7 and 10. Pups of both genotypes had similarly limited voice repertoires at PND 3. Later on, at PNDs 7 and 10, while wild-type pups emitted USVs consisting of six different syllable types, knockout pups vocalized with only two types. This developmental impairment in USV emission was rescued within 30 min by intraperitoneal OXT treatment, but quickly returned to control levels after 120 min, showing a transient effect of OXT. USV impairment was partially observed in Cd157+/− heterozygous mice, but not in Cd157−/− adult male mice examined while under courtship. These results demonstrate that CD157 gene deletion results in social communication insufficiencies, and suggests that CD157 is likely involved in acoustic communication. This unique OXT-sensitive developmental delay in Cd157−/− pups may be a useful model of communicative interaction impairment in ASD.

Highlights

There is an increasing number of patients with syndromes of multiple etiologies that are covered by the umbrella of autism spectrum disorder (ASD) (Mychasiuk and Rho, 2016) Communication ability and emotional expression are major issues in children with ASD (Eigsti et al, 2011; DiStefano et al, 2016)
Analysis of ultrasonic vocalizations (USVs) by post-hoc Turkey’s multiple comparison test showed a significantly higher call number at postnatal day (PND) 3 in Cd157−/− mice compared with Cd157+/+ controls (17 ± 2 calls/min vs. 5 ± 1 calls/min per 3-min session, respectively; P < 0.001, n = 10–15; Figure 1)
During the first postnatal week, the number of USVs in Cd157−/− mice dramatically decreased to 4 ± 2 calls/min at PND 10 (P = 0.02, χ 2 = 0.974, n = 10–15)

Summary

Introduction

There is an increasing number of patients with syndromes of multiple etiologies that are covered by the umbrella of autism spectrum disorder (ASD) (Mychasiuk and Rho, 2016) Communication ability and emotional expression are major issues in children with ASD (Eigsti et al, 2011; DiStefano et al, 2016). Interdisciplinary research platforms (including non-human models) are interested in finding relevant pharmacological treatments (Shen et al, 2016; Wei et al, 2016; Zheng et al, 2016). In this regards, oxytocin (OXT) is a promising therapy. OXT treatment rescues social behavioral deficits in animals (Jin et al, 2007; Freeman et al, 2016; Lawson et al, 2016; Teng et al, 2016), and patients with ASD during clinical trials to test its beneficial effects (Munesue et al, 2010; Althaus et al, 2016; Kosaka et al, 2016; Yatawara et al, 2016). We recently reported that under a social context, mutual interaction is significantly increased during the OXT arm of nasal administration, compared with the placebo arm, for ASD patients with intellectual disabilities (Munesue et al, 2016)

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